BACKGROUND: The escalating prevalence of obesity has made it a critical public health concern. There is an urgent need to identify naturally derived compounds with anti-obesity potential. Britanin (BRI), a bioactive sesquiterpene lactone derived from Inula species, has shown promise in metabolic disorder management, but its anti-obesity mechanisms remain uncharacterized. OBJECTIVES: Combining animal experiments and network pharmacology analysis to explore the effect of BRI in high-fat diet-induced obesity. METHODS: C57BL/6J male mice were used for experiment. A high-fat diet (HFD)-induced obese mouse model was treated with BRI (5/15 mg/kg, i.p.) to validate lipid metabolism and weight loss. Network pharmacology identified potential targets via SwissTargetPrediction, GeneCards and OMIM databases, with molecular docking (CB-DOCK) and PPI network analysis (STRING/Cytoscape). Relevant validations were conducted based on the screened targets. Additionally, a biosafety assessment was performed. RESULTS: In-vivo, 15 mg/kg BRI reduced body weight by 18%, decreased serum TG (-45%, p<0.001), TC (-37%, p<0.001) and LDL-C (-32%, p<0.01) and reversed adipocyte hypertrophy. Thirty-nine intersection targets were identified, with MAPK1, EGFR, PTGS2, MAP2K1 and MAPK8 as top hubs (degree centrality >15). BRI exhibited strong binding affinity (-7.7 to -10.3 kcal/mol) to these targets. Mechanistically, BRI exerts its anti-obesity effects by regulating key targets within the MAPK signaling pathway, particularly MAPK1 and inhibited the PPARγ, thereby blocking adipogenesis and promoting the transition of adipose tissue. CONCLUSION: BRI may alleviate obesity by regulating the Mitogen-Activated Protein Kinase signaling pathway, providing a rationale for natural compound-based obesity therapy.
Obesity is increasingly recognized as a chronic inflammatory condition, often driven by prolonged high-fat diet (HFD) consumption. Beyond causing metabolic dysregulation, obesity can disrupt immune-brain communication, contributing to the development of emotional disorders. During the early stages of HFD exposure, proinflammatory cytokines such as interleukin-1β (IL-1β), Tumor necrosis factor-alpha (TNF-α), and IL-6 are markedly elevated, but their levels typically return to baseline over time. Despite this normalization, persistent neuroinflammation and gliosis are observed, suggesting that adaptive immune mediators may play a role in chronic neuropathology. In our study using male C57BL/6 mice, 12 and 16 weeks of HFD-induced obesity increased plasma IL-17A levels, a key cytokine produced by CD4+ T helper 17 (Th17) cells, and upregulated IL-17A mRNA expression in the hypothalamus. Peripheral administration of recombinant IL-17A via intraperitoneal (i.p.) injection every 2 days for 4 weeks induced depressive and anxiety-like behaviors, accompanied by enhanced microgliosis in emotion-related brain regions and infiltration of CD4+/IL-17A+ cells in the meninges. Peripheral IL-17A administration also reduced heart rate variability (HRV), accompanied by altered HRV-derived indices, suggesting disruption of autonomic nervous system (ANS) regulation. Systemic administration of plasma derived from mice with 12-week HFD-induced obesity (OB plasma) evoked depressive and anxiety-like phenotypes, as well as ANS dysfunction. Neutralizing anti-IL-17A in the OB plasma effectively blocked these emotional and physiological impairments induced by OB plasma administration. Thus, our findings identify IL-17A as a critical mediator linking metabolic dysfunction, neuroinflammation, and emotional disorders, highlighting its potential as a therapeutic target for obesity-associated depression and anxiety.
Genetic epidemiologyKristen J Sutton, Julie E Gervis, Moomal Jatoi, Liang-Dar Hwang, Audrey E Hendricks, Debashis Ghosh, Kenneth E Westerman, Joanne B Cole
Most Mendelian randomization (MR) of dietary intake use the full set of genome-wide significant (GWS) variants in the instrumental variable (IV), likely biasing causal estimates due to pleiotropy. To characterize the common methods to handle pleiotropy in dietary intake MR, we conducted a scoping review of the literature on dietary intake MR studies. We extracted information on IV construction, assessment of pleiotropy, and sensitivity analyzes revealing that only 20% of studies used an IV with functional plausibility. In the absence of functionally-informed IVs, we tested if two-sample MR using GWS variants filtered for pleiotropic associations through phenome-wide association studies (PheWAS) could identify diet-health relationships supported by existing nutrition science, focusing on oily fish and alcohol intake, the latter of which has a functionally-informed IV for comparison (rs1229984 in the ADH1B gene). To further explore this question, we performed multivariable MR and employed MR-CAUSE. The numerous models consistently supported that oily fish reduced triglycerides. In contrast, GWS and PheWAS-filtered IVs suggested that alcohol decreased alanine aminotransferase levels, whereas the functional IV (rs1229984) found the opposite expected relationship. Isolating the direct effect of dietary intake from GWS IV remains challenging. Future work should focus on identifying functional variants impacting dietary behavior.
Developmental scienceMatti Wilks, Alexa Sacchi, Beatrice Turner, Paul Bloom
A growing body of research has aimed to map the characteristics of extraordinary altruists-such as those who have donated a kidney to a stranger. However, this research has primarily focused on adults, and we know little about the development of extraordinary altruism. While children cannot donate their organs to strangers nor large portions of their income to charity, they can choose not to eat animals. In this study we examine independent vegetarians (i.e., children who become vegetarian while being raised in meat eating families) as a potential case-study of extraordinarily altruistic motivation. In retrospective adult (Study 1) and developmental samples (Study 2) of American participants, we compare independently vegetarian children to family vegetarians and non-vegetarians on measures of empathy/compassion, disgust sensitivity, cognitive reflection, fearful facial recognition, social dominance orientation, and speciesism. We find that both independent and family vegetarians were lower in speciesism and SDO, and higher in disgust sensitivity and empathy/compassion, with these differences emerging almost exclusively in the retrospective adult sample. Crucially, and contrary to our hypotheses, we find no differences between independent and family vegetarians, and discuss potential interpretations of this null result. These data offer new insight into a small body of literature about independent vegetarians and show that similar traits are associated with both family and independent vegetarianism.
Veterinary medicine and scienceShahab Bahadoran, Shadi Vaeznia, Hossein Hassanpour
OBJECTIVES: The combination of high-altitude and heat stress promotes oxidative damage and immune dysfunction in broiler chickens. This study investigated the potential of dietary Echinacea purpurea to mitigate these detrimental effects. METHODS: In a 42-day trial, 108 one-day-old male Ross 308 broilers were randomly assigned to one of three dietary regimens: an unsupplemented basal diet (Control), or the basal diet supplemented with 0.25% (E0.25) or 0.75% (E0.75) hydroalcoholic E. purpurea extract. Birds were reared at 2100 m altitude and exposed to chronic heat stress. On Day 42, serum was analysed for nitric oxide (NO) and malondialdehyde (MDA). Hepatic relative telomere length was quantified via qPCR, and the expression of cytokine genes (IL10, IL1β, TNFα and IFNγ) was assessed by RT-qPCR. RESULTS: Dietary E. purpurea at both levels significantly lowered serum NO and MDA concentrations compared to the control group (p < 0.05). Relative telomere length was unaffected by treatment. Gene expression analysis revealed that the E0.75 group had significantly elevated transcripts of IL-10 (900% increase) and IFN-γ (351% increase), while IL-1β and TNF-α remained unchanged. Consequently, the composite pro-/anti-inflammatory cytokine ratio [(IFNγ + IL-1β + TNFα)/IL-10] was reduced in both supplemented groups (P < 0.05). CONCLUSION: Supplementation with E. purpurea alleviated systemic oxidative stress and induced a distinct immunomodulatory response, upregulating key cytokines IL-10 and IFN-γ in broilers under dual environmental stress. Telomere length in liver tissue was not preserved under these conditions. These results indicate that E. purpurea is a promising phytogenic feed additive for enhancing broiler resilience in challenging environments.
Veterinary medicine and scienceRohban Hameed, Muhammad Tahir, Rifat Ullah Khan, Sohail Ahmad, Luciana Rossi, Rasha K Al-Akeel
BACKGROUND: Soybean meal (SBM) is a major protein source in broiler diets, but its cost and dependence on a limited number of protein sources have increased interest in alternative feed ingredients. Rapeseed meal has considerable potential as an alternative protein source; however, its utilisation is constrained by antinutritional factors that can limit nutrient availability and broiler performance. Extrusion processing and exogenous enzyme supplementation may improve the nutritional value of rapeseed meal. We hypothesised that replacing part of dietary SBM with extruded rapeseed meal (ERSM), in combination with protease and non-starch polysaccharide (NSP)-degrading enzymes, would improve or maintain broiler performance and nutrient utilisation while supporting intestinal health. METHODS: A total of 320 day-old Ross 308 male broiler chickens were randomly assigned to four dietary treatments in a completely randomised design. During the finisher period (22-35 days), birds received a corn-SBM control diet or diets in which 5%, 7.5%, or 10% of SBM protein was replaced with ERSM. All diets contained identical levels of protease and NSP-degrading enzymes. Growth performance, nutrient digestibility, carcass characteristics, intestinal morphology and caecal microbial populations were evaluated to determine the effects of increasing ERSM inclusion. RESULTS: Dietary ERSM affected feed intake (p = 0.029), final body weight (p = 0.017), feed conversion ratio (p = 0.009) and mortality (p = 0.041), with the 5% and 7.5% ERSM treatments generally producing the most favourable performance. Apparent digestibility of dry matter, crude protein, crude fibre, fat and ash was improved in ERSM-fed birds (p < 0.05). Carcass yield, breast weight and thigh weight increased with ERSM inclusion (p ≤ 0.025), whereas liver weight decreased at the highest inclusion level (p = 0.034). ERSM also improved intestinal morphology by increasing villus height and the villus height-to-crypt depth ratio and reducing crypt depth (p ≤ 0.016). In addition, ERSM increased beneficial caecal bacterial populations and reduced Escherichia coli and Clostridium counts (p ≤ 0.050). CONCLUSIONS: Replacing SBM protein with 5%-7.5% ERSM in diets supplemented with protease and NSP-degrading enzymes improved growth performance, nutrient digestibility, carcass characteristics, intestinal morphology and caecal microbial balance in broilers. The findings indicate that appropriately processed rapeseed meal can partially substitute for SBM while maintaining or improving important productive and intestinal health outcomes.
Comprehensive reviews in food science and food safetyRuijun Wang, Zhiqi Li, Lina Zhang, Yuanming Pan, Zhanbiao He
The interplay between diet, gut microbiota, and host immunity is central to food science. The Lachnospiraceae family ferments dietary fibers to produce short-chain fatty acids (SCFAs), notably butyrate and propionate, with immunomodulatory potential. This critical review distinguishes established findings from hypotheses. Strain-level functional heterogeneity is substantial; findings from one genus cannot be generalized. Specific substrates (inulin, pectin, resistant starch, and arabinoxylan) and food processing methods shape SCFA profiles. Mechanistically, SCFAs regulate immunity via histone deacetylase inhibition, G-protein-coupled receptor activation, and Treg/Th17 modulation. However, most mechanistic data derive from rodent models; human evidence remains largely correlational and cross-sectional. Three major knowledge gaps exist: the lack of strain-level functional characterization, the absence of causal human intervention trials for the vast majority of Lachnospiraceae strains (with Anaerobutyricum soehngenii being the sole exception, tested only in metabolic disease), and limited translation into food systems. Regulatory barriers (generally recognized as safe [GRAS] status exists only for A. soehngenii CH106 and strictly for food use; no other strain has GRAS or qualified presumption of safety [QPS]), safety concerns (rare opportunistic pathogenicity), and technological challenges (oxygen sensitivity and viability in food matrices) further hinder development. Postbiotics (preparations of inactivated microbial cells or their components) and metabolite-based preparations (e.g., purified SCFAs or fermentation supernatants), alongside synbiotic formulations, offer practical near-term alternatives. Importantly, under the International Scientific Association for Probiotics and Prebiotics (ISAPP) definition, purified metabolites without cellular biomass do not qualify as postbiotics. We conclude that although Lachnospiraceae hold promise for immunomodulatory functional foods, current evidence does not support clinical or commercial claims. Priority research directions include longitudinal human cohorts, strain-level culturomics, and multi-omics integration. This review provides a realistic, food science-centered framework for future investigations.
Veterinary medicine and scienceHamid Valizadeh, Mehdi Taghinejad-Roudbaneh, Ruhollah Kianfar
BACKGROUND: The diet of Japanese quail (Coturnix japonica) during the critical post-hatching period (0-14 days) provides a basis for long-term productivity, but the exact lysine requirements are not well characterized in modern high-yield strains. Precision poultry nutrition requires updated amino acid (AA) recommendations that account for interactions between dietary crude protein (CP) and lysine, the reference AA for ideal protein specification. OBJECTIVES: To determine optimal lysine requirements for growing Japanese quail (0-14 days) at three CP levels (22%, 24%, 26%) using a dose-response method, and to compare linear versus quadratic broken-line models for estimating lysine thresholds. METHODS: A fully randomized factorial design used 900 Japanese quail chicks allocated to 15 dietary treatments (3 CP × 5 lysine levels: 0.95%, 1.1%, 1.25%, 1.4 %and 1.55 %). Growth performance, feed efficiency and carcass characteristics were evaluated. Lysine requirements were estimated by linear and quadratic broken-line regression using the non-linear least squares (NLIN) procedure in Statistical Analysis System (SAS) software version 9.4. RESULTS: Dietary CP and lysine levels significantly (p < 0.01) affected all growth parameters. Optimal lysine (1.4%) maximized body weight (73.93 g), weight gain (66.50 g) and protein efficiency ratio (PER) (2.70). Significant interactions (p < 0.05) occurred between CP and lysine for feed intake (FI), feed conversion ratio (FCR) and PER. Lysine requirements for weight gain using the linear broken-line model were 1.20%, 1.32% and 1.4% for 22%, 24% and 26% CP, respectively, showing superior fit (R2 = 66.24%-94.45%) compared to quadratic models. CONCLUSIONS: Lysine requirements of Japanese quail depend on dietary CP level. The linear broken-line model is more reliable than the quadratic approach. Producers should use 1.32%-1.42% lysine in starter diets, adjusting according to CP content. Future research should confirm these requirements under commercial production conditions and explore interactions with other key AAs in reduced formulae.
NMR in biomedicineJohannes Raspe, Tianxing Du, Mingming Wu, Jonathan Stelter, Martin Klingenspor, Daniela Junker, Thomas Skurk, Dimitrios C Karampinos
Brown adipose tissue (BAT) is a metabolically active tissue in humans, located primarily within the supraclavicular adipose tissue (scAT), that can be activated by cold or high-caloric meal consumption. While the changes of proton density fat fraction (PDFF) upon cold activation are well investigated, there is a knowledge gap regarding PDFF and T 2 ∗ dynamics upon meal-induced BAT activation. Therefore, the purpose of this study was to establish a robust pipeline to quantify PDFF and T 2 ∗ changes in scAT in fasting control and meal intervention experiments. To that end, a motion-robust radial stack-of-stars trajectory has been employed with a regularized iterative reconstruction algorithm, graph-cut-based water-fat separation, affine image registration and automatic neural-network-based region of interest (ROI) segmentation. Next to scAT, ROIs of subcutaneous adipose tissue (SAT) and muscle have been created to compare the results to reference tissues. Multi-echo gradient echo acquisitions were repeated in a total of ten volunteers before a break, in which the volunteers consumed an iso-caloric meal in the meal intervention experiment. After the break, repeated multi-echo gradient echo measurements were used to dynamically track the changes of both PDFF and T 2 ∗ . In the meal intervention experiment, scAT PDFF showed a stronger decrease of ∼ 1 % PDFF compared to the fasting control experiment, in which the decrease below baseline was similar to that in SAT. Furthermore, scAT T 2 ∗ exhibited a strong decrease to - 3 . 2 ms below baseline after meal intervention, while no decrease was observed in the fasting control experiment or in SAT. Considering the observed dynamic effects and their differences to the fasting control experiment, a PDFF decrease of ∼ 1 % PDFF and a T 2 ∗ decrease of ∼ 3 ms could be attributed to meal-induced activation of scAT.
Veterinary medicine and scienceRamazan Sheikh-Nazari, Kaveh Jafari-Khorshidi, Mohammad Ali Jafari
BACKGROUND: While canola seed is a valuable protein and energy source in poultry nutrition, its use is often limited by antinutritional factors that impair nutrient utilisation and bird performance. OBJECTIVES: This study investigated the effects of phytase and protease enzymes in diets containing canola seed on performance, nutrient digestibility, digestive enzyme activity, intestinal morphology, ileal microbial populations, intestinal viscosity and tibia bone mineralisation in broiler chickens. METHODS: A total of 300 male Ross 308 one-day-old chicks were used in a completely randomised design with 5 treatments, 5 replicates and 12 chicks per replicate. The experimental treatments included: control: a corn-soybean meal-based control diet without canola seed; CS-10: a diet containing 10% canola seed; CS-PRO: a diet containing 10% canola seed supplemented with protease; CS-PHY: a diet containing 10% canola seed supplemented with phytase and CS-PRO-PHY: a diet containing 10% canola seed supplemented with a combination of protease and phytase. RESULTS: Feed intake and body weight gain were significantly higher in the control and CS-PRO-PHY treatments at different experimental periods compared to the CS-10 diet (P < 0.05). Apparent metabolisable energy and the digestibility of crude fibre and ash were higher in the control group and in broilers fed CS-PHY and CS-PRO-PHY compared with birds fed the CS-10 and CS-PRO diets (P < 0.05). At Day 10, amylase and lipase activity were highest in broilers fed the CS-PRO-PHY (P = 0.001). The villus height and villus height-to-crypt depth ratio on Days 10 and 42 were significantly higher in broilers fed the control diet, the CS-PRO-PHY and CS-PHY compared to the CS-10 (P < 0.01). At Day 10, Lactobacillus populations were highest in broilers fed the CS-PRO-PHY and the control diet, and lowest in the CS-10 (P = 0.03). Duodenal and jejunal digesta viscosity was significantly higher in broilers fed the CS-10 diet compared with all other treatments (P < 0.01). Tibia weight, length and weight-to-length index of the bone in the CS-PRO-PHY treatment were significantly greater than those in the CS-10 and CS-PRO treatments (P < 0.05). Moreover, bone strength in the control, CS-PRO-PHY and CS-PHY treatments was higher than in the CS-10 treatment (P = 0.034). CONCLUSIONS: Supplementation of broiler diets containing 10% canola seed with protease and phytase, particularly in combination, effectively mitigated the negative effects of canola on nutrient digestibility, intestinal morphology, microbial balance, digesta viscosity and bone quality, leading to restoration of performance.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyGuiqiu Zhou, Mengling Chen, Lingling Zhao, Feitong Liu, Zhongbao Yue, Jingqi Zhao, Dayong Ren
Obesity and its associated metabolic disorders pose significant global health challenges. This study investigated the anti-obesity effects of Akkermansia muciniphila HHAKKα in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were administered HHAKKα orally for 8 weeks while maintained on HFD. Results demonstrated that HHAKKα significantly inhibited weight gain (5.76 g vs. 10.79 g in HFD group), with efficacy comparable to orlistat. HHAKKα intervention effectively maintained glucose homeostasis, decreased serum triglycerides and LDL-cholesterol levels, and elevated adiponectin and GLP-1 levels. Furthermore, HHAKKα significantly reduced pro-inflammatory cytokines (TNF-α, IL-1β, MCP-1) and alleviated hepatic steatosis and adipocyte hypertrophy. Mechanistically, HHAKKα modulated gut microbiota composition, increasing beneficial bacteria (Akkermansia, Roseburia, Eubacterium) while decreasing the Bacillota/Bacteroidota ratio by 55.35%. Notably, the HHAKKα intervention significantly enhanced fecal short-chain fatty acids (SCFAs) production-particularly butyrate, which was restored to approximately 1.5 times its normal level-and this effect correlated negatively with serum lipid levels and inflammatory markers. Molecular analysis revealed that HHAKKα regulated hepatic lipid metabolism by inhibiting FASN expression and upregulating PGC-1α. These findings suggest that A. muciniphila HHAKKα ameliorates HFD-induced obesity through a multi-faceted mechanism involving gut microbiota modulation, SCFA production enhancement, inflammation suppression, and hepatic lipid metabolism regulation, highlighting its therapeutic potential for obesity management.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyAli Akbar Soleimani, Masoume Aliabadi, Jamal Amri, Ghodratollah Panahi, Reza Meshkani
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major hepatic complication of obesity with a complex pathogenesis. This study aims to investigate the combined effects of empagliflozin (EMPA) and resveratrol (RSV) treatment on obesity-associated MASLD in a high-fat diet (HFD)-fed mouse model. C57BL/6J mice were fed by HFD for 23 weeks, along with treatment with EMPA (0.01% w/w), RSV (0.4% w/w), and their combination. Metabolic parameters, glucose tolerance, hepatic steatosis, inflammation, and adipose tissue morphology and function were evaluated using biochemical assays, histology, immunofluorescence, qPCR, western blotting, and 18F-FDG PET scan. Combination therapy reduced body weight gain and improved glucose tolerance more effectively than monotherapies. It significantly alleviated hepatic steatosis, as shown by decreased liver weight, triglyceride content, MASLD activity score (MAS), and serum ALT/AST levels. Co-treatment also reduced hepatic inflammation by suppressing macrophage infiltration, shifting macrophages toward an M2 anti-inflammatory phenotype, inhibiting NF-κB activation, and enhancing AMPK phosphorylation. Furthermore, the combination more effectively activated brown adipose tissue thermogenesis and induced browning in subcutaneous white adipose tissue, evidenced by upregulation of UCP1, PGC-1α, TFAM, and TMEM26, increased mitochondrial biogenesis, and enhanced cold tolerance. The combination of EMPA and RSV exerts a multi-targeted therapeutic effect against HFD-induced MASLD. This combination represents a promising novel strategy for MASLD prevention.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyJie Xu, Mengqi Zeng, Hua Li, Yiting Shen, Zhaode Feng, Weiqiang Lv, Li Cui, Ke Cao, Jiankang Liu, Zhihui Feng
Sialic acid is a well-characterized monosaccharide known to regulate early development and lifelong health, and its aberrant metabolism has been closely linked to multiple pathologies including cancer, cardiovascular disease, and neurological disorders. However, its role in early-life metabolic programming and adult metabolic homeostasis remains poorly understood. Here, we investigated Cmp-Neu5Ac synthase (CMAS), a key enzyme in the sialylation pathway, using two complementary mouse models to address this gap. In a mammary-specific Cmas knockout model, reduced milk sialyllactose levels significantly altered offspring metabolic development. Offspring nursed by CMAS-deficient dams displayed increased body weight and impaired glucose and insulin tolerance at weaning. When challenged with a high-fat diet, these offspring developed exaggerated weight gain, enhanced adipose expansion, and more severe hepatic ballooning degeneration, indicating that early-life sialylation deficiency disrupts metabolic programming and increases susceptibility to metabolic stress in adulthood. To determine whether sialylation is also essential for maintaining hepatic metabolic stability later in life, we generated a liver-specific Cmas knockout model. Deletion of Cmas markedly reduced serum sialylation and hepatic Neu5Gc-containing glycopeptides, leading to hepatomegaly, steatosis, and fibrosis, which was accompanied by activated lipogenic axis, impaired mitochondrial respiratory complex activity, increased mitochondrial fission and triggered compensatory AMPK-PGC1α signaling. Notably, CMAS deficiency sensitized hepatocytes to inflammatory stress, as evidenced by exacerbated lipid accumulation, elevated ROS production, and reduced ATP content upon LPS challenge. Together, our results demonstrate that sialylation is indispensable for both developmental metabolic programming and adult hepatic metabolic homeostasis, establishing a critical link between sialylation status and lifelong metabolic health.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyHuihui Wang, Chaoying Wang, Shuaishuai Guo, Guang Yang, Junnan Fang, Jingyi Hu, Ran Jiang, Jun Zhai, Haixia Jin, Wenyan Song, Senlin Shi, Xianju Huang, Lin Qi,…
Obesity triggers ovarian dysfunction and female infertility accompanied by granulosa cell damage. Ferroptosis, iron-dependent lipid peroxidation-mediated cell death, participates in multiple reproductive diseases, yet the molecular cascade linking metabolic obesity to granulosa ferroptosis remains undefined. Using high-fat diet obese mice, primary human granulosa cells from obese infertile patients, and KGN cell lines, we identified the nuclear receptor NR4A1 as a key mediator of obesity-induced ferroptosis downstream of PI3K/AKT signaling. Elevated NR4A1 was associated with upregulated ACSL4 and suppressed GPX4, accompanied by iron overload, lipid peroxidation, and mitochondrial collapse, impairing folliculogenesis and oocyte quality. Metformin reduced NR4A1 activation in association with PI3K/AKT signaling modulation, thereby attenuating ferroptotic injury and contributing to the restoration of ovarian function. In vivo NR4A1 agonist administration attenuated the protective effects of metformin, while ovarian-specific NR4A1 knockdown alleviated HFD-triggered ovarian ferroptosis. Single-cell RNA-seq further suggested that metformin remodels oocyte redox and folliculogenic transcriptional networks. These findings support a role for the PI3K/AKT-NR4A1 signaling pathway in driving ferroptosis during obesity-related ovarian dysfunction and suggest a potential anti-ferroptotic mechanism of metformin in this context.
Journal of the International Society of Sports NutritionMartin Fréchette, Erik Sesbreno, Louise Capling, François Bieuzen, Pascale Morin
BACKGROUND: The literature suggests that many athletes fail to meet health and sport-specific dietary recommendations which may negatively impact their overall health and performance. Moreover, completing a proper assessment of an athlete's diet is complex; the quality and validity of assessment tools are lacking in this population and resources to conduct these evaluations are limited. The Athlete Diet Index (ADI) is a validated dietary assessment tool that evaluates dietary intake and patterns of Australian athletes. However, the ADI does not consider Canadian nutrition recommendations or country-specific dietary patterns in language relevant to the population. METHODS: The cross-cultural adaptation initially began with a revision of the ADI by three experienced sport dietitians. This Canadian version was then reviewed using a modified Delphi process involving a panel of eight experienced Canadian sport dietitians. Next, the forward-backward translation method was applied to obtain the French language version. Lastly, as recommended in the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology, a pilot study with a convenience sample of Canadian athletes (n = 49) was conducted. RESULTS: The initial revision stage led to the adaptation of 67 of the 112 questions and text elements (i.e. 97 questions and 15 instructional statements) for reasons such as language (65), Canadian dietary context (35), and relevance to Canadian athletes (4). After two rounds of Delphi interspersed with a roundtable meeting, the panelists agreed to modify 56, add five, and delete four questions. The forward-backward translation process resulted in a total of 48 changes to improve terminology (32), syntax errors (9), and align with decisions of the modified Delphi panel (7). The pilot study indicated the tool was relevant/very relevant (n = 44) and easy/very easy to understand (n = 39). English and French versions were judged equivalent by a majority (80%) of the bilingual athlete participants (n = 11). CONCLUSION: The cross-cultural adaptation of the ADI resulted in a 98-question Canadian version of the dietary assessment tool supported by evidence of face and content validity and available in the language of their choice.
Tropical animal health and productionChayapol Meeprom, Ruttanachira Ruttanaprasert, Pajaree Totakul, Nantakarn Jundee, Thitima Norrapoke, Ahkarapon Nunoi, Metha Wanapat, Thiwakorn Ampapon
The aim of this study was to evaluate the effects of replacing cassava chips with culled organic sweet potato in concentrate diets on feed intake, rumen fermentation characteristics, estimated methane production, milk yield, and milk composition in dairy cows. Four multiparous Holstein Friesian cows (4 years of age; 325 ± 15 kg initial body weight) were assigned to a 4 × 4 Latin square design. The concentrate diets were formulated by progressively replacing the cassava chip fraction with culled organic sweet potato at levels of 0%, 33.3%, 66.6%, and 100%. Cows were fed concentrate twice daily (05:00 and 16:00 h) according to a concentrate-to-milk ratio of 1:2, while rice straw, minerals, and water were offered ad libitum. The experiment consisted of four 21-day periods. Feed intake was not affected by dietary treatments. Likewise, ruminal pH, temperature, ammonia-N, and blood urea nitrogen were not influenced by treatments. Total volatile fatty acid concentration decreased linearly at the highest replacement level (P < 0.05), whereas acetate, propionate, butyrate, and the acetate-to-propionate ratio were not affected. Estimated methane production decreased linearly with increasing levels of sweet potato inclusion (P < 0.05). Milk yield, fat-corrected milk, energy-corrected milk, protein, and solids-not-fat were not affected by dietary treatments. However, milk fat, total solids, and lactose increased with increasing sweet potato inclusion (P < 0.05). In conclusion, replacing cassava chips with culled organic sweet potato had no adverse effects on feed intake, rumen fermentation, or milk production, while reducing estimated methane production and improving selected milk composition parameters in lactating dairy cows.
PloS oneMehakpreet K Thind, Mary Flanagan, Sanne de Wit, Aida Glembocki, Jiali Pan, Celine Cuinat, Sharon Leung, Shamsun Nahar Shaima, Hamza Sghayare, Kinza Usmani, Mi…
Globally, almost half of all early childhood deaths are linked to severe undernutrition, herein referred to as severe malnutrition. Mortality in severely malnourished children is often attributed to common infectious diseases, including enteric infections. It has been proposed that impaired intestinal barrier function contributes to mortality, but direct evidence is limited and thus there exists a need to develop improved preclinical models to test these and other mechanistic hypotheses. In this study, we aimed to describe differences in response to enteric inflammation and infection in the colon of malnourished mice compared to well-nourished littermates. C57Bl/6 male weanlings were fed isocaloric diets, either a low 1% protein diet (LPD) or a control 18% protein diet (CPD) for 2-weeks either in combination with oral administration of dextran sodium sulfate (DSS), or Citrobacter rodentium (C. rodentium). LPD-fed mice were more susceptible to DSS or C. rodentium as evidenced by increased clinical severity scores, and reaching their humane endpoints. LPD-fed mice also showed more signs of colonic dysfunction with reduced levels of tight junction proteins, higher colonic pathogen load, and increased systemic inflammation and bacterial spread. Taken together, these observations show that malnourished animals have increased susceptibility to intestinal dysfunction caused by either chemical exposure or infection. These novel preclinical models can be used to further elucidate the processes involved in enteric dysfunction in malnutrition and to test therapies to improve intestinal repair and outcomes.
BACKGROUND: A high-fat diet (HFD) is closely associated with the progression of ulcerative colitis (UC). However, the underlying mechanisms, particularly the interplay among lipid metabolic disturbances, mitochondrial damage, and intestinal barrier dysfunction, remain poorly defined. This study aimed to elucidate the molecular mechanisms by which HFD exacerbates DSS-induced UC, with a focus on the role of the AMPK/PPARα axis in mediating lipotoxicity and mitochondrial dysfunction that promote UC progression. METHODS: A murine UC model was established in C57BL/6 mice by HFD feeding combined with DSS administration, along with an in vitro co-stimulation system using Caco-2 cells exposed to palmitic acid (PA) and lipopolysaccharide (LPS). Pathological phenotypes and molecular pathway alterations were systematically evaluated by hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), molecular biological techniques, and intervention with the specific AMPK agonist AICAR. RESULTS: HFD significantly exacerbated DSS-induced colitis, as manifested by rapid weight loss, elevated disease activity index, and destruction of mucosal tissue architecture. Mechanistically, HFD led to intestinal epithelial lipid accumulation and gut microbiota dysbiosis, which synergistically triggered oxidative stress and paradoxically suppressed AMPK phosphorylation (p-AMPK). AMPK inactivation downregulates PPARα and its downstream fatty acid oxidation enzymes (CPT1A and ACOX1), exacerbating lipotoxicity and mitochondrial ultrastructural damage. Concurrently, decreased expression of key respiratory chain subunits (NDUFS2 and MTCO2) ultimately culminates in an energy crisis. Notably, pharmacological activation of AMPK using AICAR effectively reversed p-AMPK inhibition, restored PPARα expression, and ameliorated intestinal barrier function, demonstrating that the AMPK pathway serves as a critical pathogenic driver. CONCLUSION: HFD, through lipotoxicity and microbiota-derived pro-inflammatory signals, induces paradoxical inactivation of the intestinal epithelial AMPK/PPARα axis, which subsequently blocks fatty acid oxidation, provokes mitochondrial dysfunction and ATP depletion, and ultimately leads to breakdown of the intestinal barrier. This study uncovers a novel mechanistic link among metabolism, mitochondrial function, and gut barrier integrity, providing a solid theoretical and experimental foundation for precision metabolic reprogramming-based therapies in UC patients with metabolic derangements.
Journal of developmental origins of health and diseaseWillian do Nascimento de Souza Rodrigues, Lucas Paulo Jacinto Saavedra, Paulo Cezar de Freitas Mathias
Maternal protein restriction during lactation is associated with stunted growth and hyperphagia in adult offspring, yet its long-term effects on mitochondrial uncoupling-related proteins in interscapular brown adipose tissue (iBAT) remain unknown. This study investigated how postnatal protein undernutrition affects thermogenic regulators and metabolic programming in adult males. Dams received either a low-protein (LP; 4% protein) or normal-protein (NP; 20.5% protein) diet during the first two weeks of lactation. Thereafter, the NP diet was provided to LP dams until weaning and to all offspring from weaning to PND 90. Male offspring were euthanized at postnatal day 90 for somatic, biochemical, hormonal, and iBAT UCP1 and β3-AR protein analyses. Compared with NP controls, LP offspring exhibited reduced body mass, length, and visceral adiposity, despite increased food consumption (all p < 0.0001). They also showed reduced glycemia, insulin, HOMA-β, TyG index, albumin, and HDL-c (all p < 0.05), together with increased peripheral insulin sensitivity assessed by ipITT (p < 0.05). Conversely, LP offspring exhibited increased AST activity and AST/ALT ratio (both p < 0.05) and higher hepatic cholesterol content (p < 0.01). In iBAT, UCP1 protein content was reduced (p < 0.05), whereas β3-AR remained unchanged (p > 0.05). These findings indicate that maternal protein undernutrition during lactation programmed a persistent metabolic phenotype characterized by hyperphagia, reduced somatic growth and visceral adiposity, increased peripheral insulin sensitivity, and lower iBAT UCP1 protein abundance. Collectively, these results suggest long-term alterations in energy partitioning and the iBAT molecular phenotype, although functional thermogenesis was not assessed.
Molecular biomedicineYuze Sun, Yuxuan Liu, Xiyu Chen, Shizhou Deng, Ning Zhang, Feifei Wu, Dong Fan, Yayun Wang, Yanling Yang
Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic liver diseases worldwide, characterized primarily by excessive lipid droplet (LD) accumulation in hepatocytes. Bariatric surgery, particularly sleeve gastrectomy (SG), represents the most effective intervention for reversing MASLD, although the underlying mechanisms remain incompletely understood. This study aimed to investigate the mitochondrial and lipid droplets (LDs) related molecular mechanisms by which SG ameliorated MASLD. Using a high-fat diet (HFD)-induced mouse model of MASLD, combined with SG intervention, hepatocyte-specific genetic manipulation, multi-omics analysis, and mitochondrial ultrastructural examination, we observed that MASLD was associated with a marked upregulation of perilipin 5 (PLIN5) on the LD surface and mitochondrial fission factor (MFF) on the mitochondrial outer membrane. Ultrastructural and co-immunoprecipitation (Co-IP) analyses revealed that PLIN5 and MFF formed a complex that facilitated the recruitment of LDs to mitochondria and their penetration into the mitochondrial matrix. This process ultimately led to disrupted mitochondrial fatty acid β-oxidation and structural disorganization. SG significantly downregulated PLIN5 and MFF expression, reduced LD-induced mitochondrial damage, and enhanced mitochondrial resilience to high-fat stress. These changes might contribute to the restoration of mitochondria-LD structural and functional homeostasis, ultimately reversing MASLD. Our findings indicated that aberrant upregulation of MFF contributed to MASLD progression, and SG might alleviate the disease by suppressing the MFF-PLIN5 axis to normalize mitochondria-LD interactions. These results suggested that targeting the MFF-PLIN5 axis may offer a promising therapeutic strategy for non-surgical management of MASLD.
INTRODUCTION: High intake of ultra-processed foods (UPFs) is associated with an increased risk of type 2 diabetes. However, evidence from randomised controlled trials evaluating the effect of UPF reduction on postprandial glucose responses and glycaemic variability in young adults is limited. The Ultra-Processed Food Reduction Intervention and Continuous Glucose Monitoring (ULTRA-CGM) trial aims to evaluate the effects of a UPF-reducing dietary intervention on postprandial glucose responses and glycaemic variability in healthy Korean young adults. METHODS AND ANALYSIS: This is a parallel, two-arm randomised controlled trial enrolling 50 participants (aged 20-39 years) with UPF intake ≥25% of daily energy. Following a 10-day baseline monitoring period using CGM and lifestyle diaries, participants are randomised 1:1 to a 40-minute one-on-one UPF-reducing dietary intervention or a 40-minute one-on-one standard dietary counselling based on national dietary guidelines (control). The intervention focuses on reducing UPF consumption, with participants counselled to maintain their usual total energy intake and lifestyle behaviours. After the intervention, participants undergo a 10-day CGM monitoring period and lifestyle diaries. The primary outcome is the change in postprandial glucose responses, quantified as 2-hour incremental area under the curve following meals, from baseline to postintervention. Secondary outcomes include changes in glycaemic variability metrics (coefficient of variation, SD, mean amplitude of glycaemic excursions, glucose spike frequency), time-in-range metrics, body weight, waist circumference, body composition, blood pressure and handgrip strength. For the analyses, between-group differences will be evaluated using analysis of covariance adjusting for baseline values, with daily CGM data analysed using linear mixed-effects models. This trial will provide evidence on whether targeted reduction of UPFs improves postprandial glucose control and glycaemic variability in healthy young adults. ETHICS AND DISSEMINATION: This study is approved by the Korea University Institutional Review Board (KUIRB-2025-0600-05). It will be conducted in accordance with the principles of the Declaration of Helsinki and the principles of the International Conference on Harmonisation Good Clinical Practice guidelines. Results will be disseminated through publications, academic conferences, PhD dissertation and social and lay media. TRIAL REGISTRATION NUMBER: NCT07175701.
Journal of molecular histologyLijun Cao, Yongna Zhao, Ping Li
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by dysregulated hepatic lipid metabolism and persistent inflammatory remodeling. Apigenin has lipid-regulatory and anti-inflammatory activities, but the molecular basis linking these effects remains incompletely understood. This study investigated whether SMAD4-associated signaling contributes to the coordinated regulation of hepatocyte lipogenesis and macrophage inflammatory activation by apigenin. C57BL/6J mice were fed a high-fat diet (HFD) to establish MASLD and treated with apigenin. Palmitic acid (PA)-treated HepG2 cells and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were used as complementary in vitro models. Hepatic lipid accumulation, inflammatory responses, macrophage phenotype, and SMAD4-associated signaling were evaluated using biochemical assays, histological staining, ELISA, RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. Molecular docking was used to predict the potential interaction between apigenin and SMAD4, a cellular thermal shift assay (CETSA) was performed in HepG2 cells to assess cellular target engagement of SMAD4 by apigenin, and SMAD4/Smad4 overexpression was used to evaluate functional involvement. Apigenin alleviated HFD-induced liver injury, dyslipidemia, and hepatic lipid deposition and suppressed the SREBP-1c/FAS/ACC lipogenic program in mouse liver and PA-treated HepG2 cells. Apigenin also reduced hepatic CD68-positive macrophage accumulation, decreased CD86 and iNOS expression and pro-inflammatory cytokine levels, and attenuated M1-like inflammatory activation in vivo and in LPS-stimulated RAW264.7 macrophages. Molecular docking predicted a favorable interaction between apigenin and SMAD4, while CETSA demonstrated increased thermal stability of SMAD4 following apigenin exposure in HepG2 cells, supporting cellular target engagement in this cellular context. Apigenin further attenuated SMAD4-associated signaling, whereas SMAD4/Smad4 overexpression partially counteracted its anti-lipogenic and anti-inflammatory effects in HepG2 cells and RAW264.7 macrophages, respectively. These findings indicate that apigenin alleviates HFD-induced MASLD by coordinately suppressing hepatocellular lipogenesis and macrophage-associated inflammatory activation and suggest that SMAD4-associated signaling contributes to these metabolic and inflammatory effects.
Gut microbesNicole M Simm, Georgina M Williams, Sophie Fowler, Katherine Barlow, Benazir Carter, Nicholas J Talley, Simon Keely, Kerith Duncanson, Emily C Hoedt
Understanding and identifying relationships between dietary intake and the gastrointestinal microbiome can provide critical information for optimization of human health. However, methodological approaches largely differ and can impact research findings. Here we outline differences in reported diet-microbiome associations from a range of studies utilizing comparable statistical methods. From a subset of 25 studies using comparable methodology, only 3% of reported diet-microbe associations were common across more than one study. As such, we emphasize the inconsistencies of findings within the literature and wider implications of these differences.
PloS oneSaba Karimi, Sara Kaveh, Sara Emamgholipour Sefiddashti, Samaneh Akbarpour, Sajjad Dorri, Yosra Azizpour
INTRODUCTION: Red meat consumption is an important dietary factor in hypertension management, yet its distribution may vary across socioeconomic groups. This study examines wealth-related inequality in red meat consumption among hypertensive adults in Iran. OBJECTIVE: To quantify wealth-related inequality in red meat consumption among hypertensive adults in Iran and explore factors associated with this inequality. METHODS: Utilizing data from the 2021 Iranian STEPS survey, a nationally representative sample of 9,024 hypertensive adults was analyzed. Excessive consumption was defined as consuming red meat four or more times per week. Wealth-related inequality in consumption was then assessed using a wealth index derived from principal component analysis (PCA) of household assets and living conditions. Wagstaff decomposition analysis was employed to disaggregate the concentration index (CI) and explore the contribution of each factor to the observed inequality. RESULTS: The hypertensive adults included in the study had a mean age (95% CI) of 56.1 years (55.8, 56.5). The proportion of excessive red meat consumption was 16.5%. A significant wealth-related inequality was observed in excessive red meat consumption (CI = 0.179, p < 0.001), indicating that excessive consumption was concentrated among wealthier individuals. Wagstaff decomposition analysis showed that higher educational attainment (≥12 years) was the largest contributor to the observed inequality (20.6%), followed by unpaid work (6.8%), unemployment (4.4%), and age 40-59 years (4.2%). Overall, the included determinants explained 29.4% of the observed inequality. CONCLUSION: This study identified significant wealth-related inequality in excessive red meat consumption among hypertensive adults in Iran, with higher consumption concentrated among wealthier groups. Educational attainment was the largest contributor to the observed inequality. Policies should consider socioeconomic differences in dietary behaviors and promote targeted nutrition interventions to reduce cardiovascular risk and improve dietary equity.
Metabolomics : Official journal of the Metabolomic SocietyEzequias Castillo-Lopez, Markus Aigensberger, Rana Muhammad Atif, Patrick Biber, Thomas Hartinger, Sabina Raykova, Alejandra Guerrero-Lavin, Nicole Reisinger, …
INTRODUCTION: The combined effects of increased dietary concentrate and hindgut starch supply on the cow metabolome remain poorly understood. OBJECTIVE: To evaluate the impacts of high concentrate feeding and the impacts of increased hindgut starch supply on the metabolome of rumen, feces and blood of Holstein cows. METHODS: Either a 40% (Control) or a 65% concentrate diet (High) was fed. In addition, cows were abomasally infused with either water or starch (3 kg/day). Metabolomic analysis of rumen, feces and blood were performed with HPLC-MS/MS and anion exchange chromatography coupled to high-resolution mass spectrometry. RESULTS: Ruminal pH duration < 5.8 was 69 and 249 min/day for Control and High, respectively; fecal pH was 6.58 and 6.33 for water- or starch-infused cows, respectively. Independent of abomasal starch infusion, High increased ruminal concentration of several amino acids, nucleosides, and lipid-related metabolites, and enriched metabolic pathways for purine metabolism, urea cycle and amino acid metabolism. In feces, both High and abomasal starch infusion increased metabolites related to fatty acid and nitrogen metabolism, and enriched pathways for bile acid biosynthesis, amino acid metabolism, α-linolenic acid and biotin metabolism. In blood, Control enriched metabolic pathways for amino sugar metabolism, aspartate metabolism, fatty acid biosynthesis and malate-aspartate shuttle, regardless of abomasal starch infusion. CONCLUSION: High enhanced metabolic pathways mainly for ruminal nitrogen metabolism. Both High and abomasal starch infusion influenced fecal metabolic pathways; whereby, the increased ethanolamine suggests its potential as a biomarker for gut acidosis. Compared to abomasal starch infusion, High had greater impacts on the blood metabolome.
MedicineYuting Wu, Ziman Jiao, Yuxin Liu, Yunhao Zhou, Haiyu Li, Xin Chen, Guanghui Liu
The association between oxidative balance score (OBS) and age-related macular degeneration (AMD) in US adults currently remains unknown. This research aimed to explore the specific association between OBS and AMD. OBS was acquired based on dietary and lifestyle factors, including 16 nutrients and 4 lifestyle components. Weighted logistic regressions were used to explore the associations between OBS and the prevalence of AMD. Subgroup analyses and interaction tests were conducted to understand the relationships across different populations. Furthermore, linear or nonlinear correlations were assessed by spline smoothing and threshold effect analyses. A total of 2408 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES) in the United States. This research demonstrated a negative association between OBS and AMD; an increase in OBS may reduce the AMD prevalence. Specifically, lifestyle OBS showed the most consistent inverse association with AMD. Higher lifestyle OBS was associated with lower odds of prevalent AMD, while total and dietary OBS showed directionally inverse but non-significant associations after full adjustment. This negative association varied significantly across different subgroups, with more pronounced effects observed in younger or unmarried individuals, non-Hispanic Black races, and those with diabetes or hyperlipidemia within each stratum. Specifically, it was found that this association effect of OBS with AMD was observably greater in people aged 40 to 49 years [OR = 1.05 (0.91, 1.21), P for interaction = 0.0191], unmarried people [OR = 1.38 (0.83, 2.30), P for interaction = 0.0125], non-Hispanic Black [OR = 1.16 (0.90, 1.49), P for interaction = 0.0215], patients with diabetes [OR = 1.25 (1.01, 1.56), P for interaction = 0.0228], and people without hyperlipidemia [OR = 1.67 (1.23, 2.28), P for interaction = 0.0338]. Furthermore, no statistical evidence of nonlinear association was identified using spline smoothing. There exists a possible negative association between OBS and AMD in US adults. OBS is associated with AMD prevalence.
Cardiovascular-kidney-metabolic (CKM) syndrome represents a pathophysiological continuum from metabolic dysregulation to cardiovascular injury. However, whether dietary interventions confer stage-specific benefits remains unknown. We aimed to examine the association between flavonoid intake and CKM stages and to assess baseline intake and mortality across stages. We analyzed 10,754 US adults from National Health and Nutrition Examination Survey (2007-2010, 2017-2018). CKM stages (0-4) were defined at baseline. Flavonoid intake was assessed via two 24-hour recalls. Mortality was ascertained using the National Death Index linkage in December 2019 (median follow-up, 9.6 years). Cross-sectional associations with CKM stages were examined using multinomial logistic regression. Prospective associations with all-cause, cardiovascular, and cancer mortality were examined using survey-weighted Cox models stratified by CKM stage. Restricted cubic splines and weighted quantile sum regression further characterized dose-response relationships and mixture effects. Higher flavonoid intake was associated with lower odds of advanced CKM stage (stage 2 vs 0: Q4 odds ratio: 0.53; 95% confidence interval [CI]: 0.33-0.83). Stage-specific mortality associations emerged: Q4 reduced cancer mortality in stages 1 to 2 (hazard ratio [HR] = 0.60; 95% CI: 0.37-0.96) and all-cause mortality in stages 3 to 4 (HR = 0.80; 95% CI: 0.65-0.99). An L-shaped dose-response showed an inflection at 218.8 mg/d; below this, each 50 mg/d increment reduced the risk by 9% (HR = 0.91). The inverse associations were stronger in adults aged <65 years and nonusers of lipid-lowering medications (P < .05). Weighted quantile sum regression identified anthocyanidins (50.6%) and flavones (24.8%) as primary contributors to cancer mortality reduction in the early stages, whereas isoflavones contributed 49.7% to all-cause mortality protection. These findings suggest potential stage-specific benefits: anthocyanidin- and flavone-rich diets may warrant further investigation for prevention, whereas isoflavone-focused intake may have relevance for survival in advanced stages. The observed threshold of approximately 219 mg/d provides a potential quantitative target for future research.
The causal relationship between strict dietary patterns and nonspecific renal failure (RF) remains a subject of intense clinical debate. Epidemiological observations are frequently confounded by post-diagnostic health-seeking behaviors and metabolic comorbidities. This study aimed to investigate the genetically predicted causal impacts of both dietary diversity (unrestricted eating) and specific carbohydrate-restricted diets (avoidance of sugar and wheat) on the risk of RF. Summary-level genome-wide association study data were leveraged. We first conducted univariable Mendelian randomization (MR) to evaluate the overall causal effect of a comprehensive dietary pattern ("Eat all" encompassing eggs, dairy, wheat, and sugar). Subsequently, multivariable MR was employed to disentangle the independent effects of individual dietary exclusions, mutually adjusting for genetic liabilities of overlapping eating habits. Instrument strength was verified using F-statistics. MR results were expressed as odds ratios with 95% confidence intervals. In univariable MR, a genetically predicted balanced dietary pattern ("Eat all") demonstrated a profound, highly significant causal protective effect against RF (Inverse variance-weighted: Beta = -2.064, standard error (SE) = 0.615, P = .00079) (odds ratios = 0.1269; 95% confidence intervals: 0.038-0.424). Conversely, in the multivariable MR model conditioning on overlapping dietary avoidances, specific carbohydrate restrictions emerged as independent hazards; "never eat sugar" (Estimate = 0.624, SE = 0.277, P = .026) and "never eat wheat" (Estimate = 2.292, SE = 1.094, P = .038) were both independently associated with an elevated susceptibility to RF. Restrictions on eggs and dairy products showed no significant independent effects. Genetically predicted dietary diversity exerts a robust renoprotective effect, whereas the extreme exclusion of primary carbohydrate sources (sugar and wheat) independently drives RF risk. These findings suggest that long-term restriction of key macro-nutritional vectors may disturb renal metabolic homeostasis, underlining the need for caution before adopting untargeted elimination diets.
Journal of human nutrition and dietetics : the official journal of the British Dietetic AssociationSteph Sloan, Jane Sadler, Sharleen Woods
BACKGROUND: Eating disorders (EDs) are associated with significant physical, psychological, and social impairments. Dietitians play a vital role in ED treatment, yet their impact is underreported. AIM: To evaluate the pilot implementation of a novel dietetic outcome measure tool within a community ED service, with a focus on feasibility and acceptability. METHODS: A mixed-methods evaluation was conducted over six months in 2024. Quantitative data were collected using a novel dietetic outcome measure tool being piloted within the service and analysed descriptively. Qualitative data were collected through semi-structured interviews with dietitians piloting the tool and analysed using reflexive thematic analysis. RESULTS: Quantitative outcome data from 102 patients were analysed to describe service level referral patterns, intervention focus, proposed outcomes, and perceived outcome achievement. Restrictive dietary patterns and malnutrition were identified as common dietetic concerns. Improving nutritional status and eating patterns were the most frequently identified dietetic outcomes. Outcome status was recorded for 54% of patients. Of those, twenty-six (47%) had a recorded outcome as 'met,' 21 (38%) as 'partially met,' and 8 (15%) as "not met." Qualitative findings are presented across 3 themes: (1) demonstrating professional value through outcome monitoring, (2) practical and organisational barriers to embedding outcome monitoring, and (3) balancing meaningful data collection with clinician burden. CONCLUSION: Participants were supportive of routine outcome monitoring in principle. However, the absence of clearly defined outcome indicators and associated data limited the tool's ability to meaningfully evaluate the intervention's effectiveness. Improved integration within existing electronic systems, combined with clearer outcome indicators and complementary qualitative approaches, may reduce clinician burden while enhancing the feasibility, acceptability, and value of routine outcome monitoring within ED dietetic services.
OBJECTIVE: The Mediterranean Diet (MedDiet) is a plant-rich dietary pattern associated with favourable adiposity profiles, making it a relevant model for studying obesity risk in children and adolescents. This study aims to investigate the association between adherence to the MedDiet and risk of obesity in children and adolescents. METHODS: An extensive search in databases PubMed/Medline, Scopus, Web of Science Core Collection, the Cochrane Library and Google Scholar up to October 2025 was conducted. Cohort studies which reported means and standard deviations for the body mass index (BMI) levels and MedDiet adherence scores, and crude and adjusted odds ratios (OR) for overweight or obesity among the children with high and low adherence to the MedDiet were eligible for inclusion. RESULTS: Twenty three articles (26 studies) met the inclusion criteria. Results demonstrated that the mean BMI levels in children adhering to the MedDiet were significantly lower than those who did not adhere to it (weighted mean difference [WMD] = -0.42 kg/m2, 95% CI: -0.61, -0.23, I2 = 65.15%, p < 0.001). Additionally, results indicated that children with overweight had a lower mean adherence score compared to children with normal weight (WMD = -0.44 scores, 95% CI: -0.76, -0.12, I2 = 85.95%, p < 0.001). CONCLUSION: This meta-analysis highlights that greater adherence to the MedDiet was associated with lower odds of obesity among children and adolescents. However, these findings should be interpreted cautiously because the evidence was entirely cross-sectional, heterogeneity was substantial across several pooled analyses and some estimates were sensitive to exclusion of individual studies.
AIM: Aberrant activation of dynamin-related protein 1 (Drp1) promotes excessive mitochondrial reactive oxygen species (mtROS) production; however, whether the Drp1-mtROS pathway mediates the renoprotective effects of aerobic exercise remains unclear. METHODS: High-fat diet (HFD)-fed mice were subjected to aerobic exercise or were intraperitoneally injected with the Drp1 inhibitor Mdivi-1 for 8 weeks. Fat mass, serum biochemical parameters, renal histopathology, mtROS production, oxidative stress-related markers, mitochondrial ultrastructure, mitochondrial membrane potential, ATP content, and protein expression were assessed. In parallel, Drp1 was knocked down in palmitic acid (PA)-treated HK-2 cells to further evaluate the role of the Drp1-mtROS pathway in lipid overload-induced renal tubular cell injury. RESULTS: Aerobic exercise reduced body weight and fat mass, improved circulating lipid profiles, and decreased serum creatinine and blood urea nitrogen levels in HFD-fed mice. Exercise also alleviated renal tubular injury, mesangial expansion, interstitial fibrosis, podocyte foot process effacement, and renal lipid accumulation. Mechanistically, aerobic exercise suppressed Drp1 phosphorylation at Ser616, reduced renal mtROS production and oxidative stress, improved mitochondrial morphology, restored mitochondrial membrane potential and ATP production, and modulated the expression of lipid-metabolism-related proteins. Pharmacological inhibition of Drp1 with Mdivi-1 largely reproduced the metabolic, mitochondrial, and renoprotective effects of aerobic exercise. Furthermore, Drp1 knockdown attenuated PA-induced mtROS accumulation, oxidative stress, mitochondrial dysfunction, and lipid deposition in HK-2 cells. CONCLUSION: Aerobic exercise exerts a protective effect on the kidneys of HFD-fed mice, at least in part, by inhibiting the Drp1-mtROS pathway. This provides insights into the benefits of aerobic exercise in obesity-related nephropathy.
Journal of human nutrition and dietetics : the official journal of the British Dietetic AssociationLeah Seamark, Olivia Radcliffe, Marianne Williams, Jim Gotto, Bridie Watson, Jenna Trudgeon, Sue Reeves, Yvonne Jeanes
INTRODUCTION: The only treatment for coeliac disease is the exclusion of all gluten from the diet. Adherence to a gluten free (GF) diet requires knowledge acquisition and changes in behaviours. The service evaluation aimed to evaluate the impact of a dietitian-led webinar for adults with coeliac disease. METHODS: The pre-recorded dietitian-led webinar had been developed by specialist dietitians and gastroenterologists and was integrated into a patient pathway. A pre- and post-webinar online survey was designed to evaluate the impact of the webinar for adult patients with coeliac disease. Patients were invited to complete an online survey prior to accessing the webinar. Four weeks later, the patients were invited to complete the post-webinar survey. RESULTS: The webinar was accessed by 1050 adults with coeliac disease, of which 57% were diagnosed within the preceding 8 weeks. In patients who completed both surveys, there was a significant improvement in confidence (p < 0.001) and knowledge (p < 0.001) to follow a GF diet (n = 165). Among patients who reported gastrointestinal symptoms on gluten ingestion (n = 71), a greater proportion reported satisfactory symptom relief after watching the webinar (p = 0.02). Behaviours to minimise gluten ingestion were positively impacted, whereby a higher proportion of patients reported to 'doing things to avoid eating gluten when preparing in the home' and 'having GF foods on hand while they are out' (p < 0.05). CONCLUSION: The dietitian-led webinar enabled timely access to high-quality resources from specialists. Access to the webinar positively impacted knowledge and behaviours to minimise gluten ingestion. This is a practical and inexpensive solution to enable specialist dietitians to utilise their skills and finite time for appointments with patients with more complex presentations.
Molecular nutrition & food researchDiene France de de Souza, Gabriel Cipriano Rocha, Dairon Pérez Fuentes, Lucas Eduardo Oliveira Porto, Pedro Vitoriano Oliveira, Marliane de Cássia Soares da Si…
Selenium plays an important role in antioxidant defense and metabolic regulation. This study evaluated the effects of dietary supplementation with non-enriched and selenium-enriched Pleurotus ostreatus mushrooms, as well as selenized yeast, on selenium deposition and antioxidant responses in piglets, a relevant model for human nutrition. Sixty-four weaned piglets were fed control or supplemented diets for 21 days. Growth performance was not affected, indicating that the treatments were well tolerated. Selenium was higher in the loin of the supplemented groups than in the control group, whereas selenium concentration in the liver showed a numerical, but nonsignificant, increase in supplemented groups (p = 0.08), and no differences were observed in the kidney. Hepatic antioxidant activity was differentially modulated by dietary treatments. Glutathione peroxidase activity increased in all supplemented groups, whereas catalase activity increased only in piglets receiving selenium-enriched mushroom or selenized yeast, and superoxide dismutase activity increased only in the selenium-enriched mushroom group. Nitrite levels were reduced in all supplemented groups, while plasma antioxidant parameters remained unchanged. These findings indicate that dietary supplementation modulated hepatic antioxidant responses, although the relative contributions of selenium enrichment and mushroom bioactive compounds could not be determined. Trial Registration Number and Date of Registration: 106/2018.
Health promotion journal of Australia : official journal of Australian Association of Health Promotion ProfessionalsLaura J Kennedy, Sara F L Kirk, Alisson Dykeman, Meaghan Sim, Jeanna Parsons Leigh, Catherine L Mah
BACKGROUND: Healthy eating policies are of growing importance to the management of retail food environments in healthcare (e.g., hospital cafeterias). Several researchers have begun to analyse health promoting benchmarks within these policies. However, little is understood about the relationship between policy and continuous quality improvement (CQI) for health promotion in healthcare. Furthering our understanding of benchmarks within these policies could provide insight into how we can measure and create standards in health promotion. This policy analysis examined publicly accessible healthcare healthy eating policies in Canadian health authority jurisdictions, up until November 22, 2022. METHODS: Data was extracted using a monitoring and evaluation framework for evaluating nutrition policies in publicly funded institutions, with adaptations based on organisational CQI concepts. Policy components analysed included: policy design, nutrient profiling systems, nutrition standards, evaluation, and monitoring. A second reviewer independently extracted data and peer debriefing was completed on the extractions. RESULTS: This analysis identified five healthy eating policies meeting the inclusion criteria, from Alberta, British Columbia, Newfoundland and Labrador, Nova Scotia, and Winnipeg, Manitoba. Policies included nutrient profiling, including benchmarks for selling healthy, moderately healthy, and less healthy food and beverages. Other benchmarks were mentioned but contained fewer indicators (e.g., fundraising, catering, and advertising). Policies included benchmarks about product and placement (e.g., healthier items in visible places) but less about price. The included policies promoted collaboration amongst healthcare providers but lacked details about evaluation and monitoring. CONCLUSION: This policy analysis suggests that different healthcare settings may require different benchmarks, tailored to their contexts. Furthermore, standardisation may not be optimal if further experimentation is needed to identify benchmarks for health promotion practices, as is common in healthcare CQI. Policy implementation requires a combination of top-down and bottom-up approaches, and collaboration with multiple partners may be necessary for success. Benchmarking processes are a potential strategy for understanding improvements to other aspects of the food environment beyond nutrient standards. SO WHAT: CQI and retail food environments each focus on customer satisfaction and costs, thus sharing alignments. CQI benchmarking processes are a potential strategy for understanding improvements to other aspects of the food environment beyond nutrient standards. Further exploration is needed to implement and monitor benchmarks over time.
Asia Pacific journal of clinical nutritionXin Zhang, Zhe Gao, Jiang-Feng Feng, Xin-Gang Wu
BACKGROUND AND OBJECTIVES: To develop and validate a machine learning model to predict the risk of psoriasis based on 45 dietary nutrients. METHODS AND STUDY DESIGN: 12,749 participants from the National Health and Nutrition Examination Survey from 2009-2014 were included and their demographic, lifestyle, health status, and dietary nutrient-related information is collected. Imbalanced data were processed using the syn-thetic minority oversampling technique (SMOTE). After removing the covariate features, important features were further screened using the Boruta algorithm and six machine learning models were constructed including Random Forest (RF), Light Gradient Boosting Machine (Light GBM), Kernel K-Nearest Neighbor (K-KNN), L Naive Bayes, Support Vector Machine (SVM) and Extreme Gradient Boosting (XGBoost). The performance of the models was evaluated using benchmarking and the area under the ROC curve (AUC) was the main evaluation metric to choose the optimal machine learning model. Shapley additive explanation (SHAP) values were computed to evaluate each feature's prediction role in the mode. RESULTS: The Boruta algorithm screened 10 baseline features and 23 dietary nutrient features, and six machine learning models were developed based on them. Compared with other machine learning models, XGBoost demonstrated superior prediction ability. SHAP analysis showed that theobromine, lycopene, caffeine, vitamin D, dietary fiber and vitamin E were the key features that influenced the prediction results. CONCLUSIONS: The machine learning (ML) algorithm constructed a prediction model for psoriasis by incorporating baseline features and dietary nutrient features. The SHAP values indicate the dominant role of dietary nutrients in the model.
Journal of human nutrition and dietetics : the official journal of the British Dietetic AssociationRebekah Sandhu, Delara Saran, Treeva Elliott
INTRODUCTION: Dietitian managers are routinely asked to provide recommendations for dietitian staffing ratios (i.e., the number of patients a dietitian 1.0 full-time equivalent (FTE) position can adequately serve). These recommendations are used as a benchmark when advocating for improving dietitian service levels, future hospital planning, and ultimately guide the FTE for which the department is budgeted. To date, there is limited empirically based evidence supporting dietitian staffing ratios for multiple care areas. The purpose of this quality improvement project is to develop consensus on the dietitian staffing ratios for inpatient, ambulatory, and long-term care areas within a large Canadian health authority. METHODS: A modified RAND/UCLA method of consensus was used. A draft document of dietitian staffing ratios was informed by a literature review. Next, iterative rounds of anonymous surveys and virtual meetings were conducted until consensus on the dietitian staffing ratios for each care area was achieved. Consensus was defined as > 70% of respondents indicating they rated an item at least slightly agree on a 7-point Likert scale. RESULTS: Eighty percent (12/15) dietitian leaders participated in the consensus process. The leaders had an average of 5.8 ± 6.3 years experience supervising a median of 8.0 FTE [1-42] of dietitian positions. Consensus was achieved after 3 rounds of surveys and meetings. The final document provides dietitian staffing ratios for 35 different practice areas. CONCLUSION: This quality improvement project is the first to provide a comprehensive list of dietitian staffing ratios for inpatient, outpatient, and long-term care areas. It provides dietitian managers in other locations with insight into a process by which they could produce their own locally relevant dietitian staffing ratios.
Physiological reportsNatalie Acosta-Castellanos, Shelly Tiede, Christopher J Byrd, Pawel Borowicz, Jennifer M Young, Eric P Berg
Our objective was to evaluate body composition and muscle insulin receptor concentration resulting from consumption of a low-carbohydrate, high-fat diet using swine as a surrogate for humans. Two treatments, a control standard swine feed (CON; n = 7) and test diet where beef tallow replaced the corn carbohydrate (LCHF; n = 8), were fed for 32 days to post-pubertal gilts (Landrace × Yorkshire). Body weight (BW), subcutaneous fat (FD), daily gain (ADG), daily feed intake (ADFI), and fasting blood chemistry were measured. Organ weights, and pancreas, longissimus, and semimembranosus samples were collected from three gilts per treatment. LCHF gilts had reduced ADG, ADFI, FD, and visceral fat (p = 0.09, 0.04, 0.06, and 0.03; respectively) with similar BW (p = 0.18). Blood chemistry parameters were not affected but for fasting glucose, which tended to be higher for LCHF (p = 0.054). The percentage (p = 0.09) and number (p = 0.07) of active pancreatic β-cells tended to be higher for LCHF gilts, as was the concentration of semimembranosus insulin receptors (p = 0.04). Short-term consumption of a low-carb, high-fat diet improved body composition, insulin production mechanics, and muscle insulin receptor density in a swine biomedical model.
Applied psychology. Health and well-beingHaide Chen, Jianxiong Zhang, Yixing Yang, Yang Zheng, Xiaowei Chu
The prevalence of adolescent obesity is closely linked to excessive consumption of high-calorie foods. Although extensive research has demonstrated the influence of emotions and emotion regulation strategies on eating behavior, little is known about the specific role of socially induced negative affect. Based on the Incentive Sensitization Theory of Addiction and the cognitive mechanisms of emotional stimuli processing, the present study recruited junior high school students and conducted two experiments to examine whether socially induced negative affect leads to a greater increase in high-calorie food intake among adolescents compared to nonsocially induced negative affect, as well as to explore the role of emotion regulation strategies. Experiment 1 showed that exposure to socially induced negative affect led to a significantly greater increase in high-calorie food intake compared to both nonsocially induced negative and neutral affective conditions. Experiment 2 showed that participants who used cognitive reappraisal during socially induced negative affect chose significantly less high-calorie food than those who used expressive suppression. The results demonstrate that socially induced negative affect influences adolescent high-calorie food intake and the specific use of cognitive reappraisal in regulating emotion-driven consumption. The present study extends theoretical understanding of social affective influences on dietary behavior and provides actionable insights for developing targeted emotion-regulation interventions to promote health for adolescents.
The gut microbiota plays a critical role in regulating intestinal lipid metabolism, yet the mechanisms governing microbiota-host interactions during lipid uptake remain unclear. Here, we examined the relationship between fat digestibility and gut microbial composition, and found that piglets with higher apparent crude fat digestibility exhibited enhanced lipid absorption and oxidation, accompanied by reduced abundance of Clostridium butyricum in the ileal mucosa. Furthermore, oral administration of C. butyricum suppressed intestinal lipid absorption and oxidation by inhibiting PPARα signaling. Mechanistically, extracellular vesicles (EVs) derived from C. butyricum can enter intestinal epithelial cells and mediate the anti-lipid absorption effects by delivering miRNA-like RNAs (milRNAs), particularly milRNA-3020179, which primarily targeted host genes including PPARα and Rxra. Supplementation with C. butyricum or its EVs prevented lipid accumulation and attenuated the development of metabolic abnormalities in high-fat diet-fed mice, whereas deletion of milRNA-3020179 in C. butyricum abolished its effects on lipid deposition in intestinal organoids. Collectively, these findings identify C. butyricum-derived EV milRNAs as candidate microbial regulators of host lipid metabolism through modulation of PPARα signaling, providing insights into microbiota-driven control of intestinal lipid homeostasis.
Journal of mass spectrometry : JMSEleonora Rollo, Alexandra Schamann, Maria Doppler, Alexandra Malachová, Rudolf Krska, Michele Suman
Based on previous experience and current knowledge, it is assumed that mycotoxins contaminating raw materials could be degraded or modified due to exposure to thermal and mechanical conditions during food processing, potentially resulting in degradation and/or conversion products. Nowadays, most of the information on the novel degradation products of mycotoxins is still missing; the identification and characterization of their structure and their toxicity potential is of high interest for risk assessment strategies. In the present study, the fate of aflatoxins and fumonisins during the production of gluten-free pasta made from maize flour was investigated. Gluten-free pasta was produced from both spiked dough and naturally contaminated flour, processed under pilot plant conditions that mimic the industrial conditions, resulting in a technologically feasible product. Possible degradation products of the spiked mycotoxins were identified using an untargeted stable isotope labelling liquid chromatography high-resolution mass spectrometry approach. No degradation product of aflatoxin B1 was detected above the detection limit of the experimental setup, and only one possible degradation product of fumonisin B1 or B2 at very low levels was found. The results may suggest the stability of these mycotoxins under the production conditions of gluten-free pasta.