Elevated postprandial glycaemic excursions contribute to cardiometabolic disease risk, highlighting the importance of dietary strategies to attenuate postprandial glycaemia for prevention. Chestnut (Castanea spp.) is rich in dietary fibre, resistant starch and bioactive (poly)phenols that may modulate carbohydrate digestion, yet evidence in human studies remains limited. We investigated the effects of a chestnut flour-enriched bread on postprandial glycaemic and insulinaemic responses in healthy adults. In a randomised crossover trial, fourteen healthy participants consumed isocaloric meals providing 50 g available carbohydrate as either chestnut flour-enriched bread (50% chestnut flour/50% wheat flour) or control bread (100% wheat flour), following an overnight fast. Capillary blood glucose and insulin were measured over 180 min, and incremental area under the curve (iAUC) was assessed for each. The (poly)phenol composition of the wheat and chestnut flours and the control (wheat only) and chestnut flour-enriched breads was characterised using RP-HPLC-HRFTMS. Chestnut flour-enriched bread, containing (+)-catechin, myricetin, gallic, gentisic and p-coumaric acids (∼480 mg total (poly)phenols), significantly reduced glucose iAUC by 27% compared with control bread (∼100 mg total (poly)phenols) (p = 0.0319, paired t-test; main effects of the meal: p = 0.0243, ANOVA). Glucose concentrations were 16% lower at 120 min (p = 0.0131) and 14% lower at 150 min (p = 0.0071). Total insulin exposure did not differ between the meals, but chestnut enrichment reduced the insulin peak time by approximately 24 min (p = 0.0430). Partial substitution of wheat flour for chestnut flour in bread significantly attenuated postprandial glycaemia in healthy adults, mainly by lowering late-phase glucose excursions without raising insulin demand. These findings support the potential of chestnut flour as a functional ingredient for improving glycaemic control.
Replacing 50% wheat flour with chestnut flour in bread lowered postprandial glucose iAUC by 27% and shifted peak insulin 24 minutes earlier in healthy adults ( n = 14). Figure produced using gemini.google.com and edited in Microsoft PowerPoint.
Obesity is a major global health concern that significantly increases the risk of chronic metabolic diseases, including type 2 diabetes and cardiovascular diseases. This study investigated the ameliorative effects of D-tagatose on glucose and lipid metabolic disorders induced by a high-fat and high-sucrose diet (HFHSD) in obese rats, and systematically explored the underlying mechanisms through a combination of biochemical, histopathological, gut microbiomic, and serum metabolomic analyses. The results demonstrated that D-tagatose significantly suppressed body weight gain and fat accumulation. Compared with the control group, the HFHSD induced pronounced glucose and lipid metabolic disorders. Compared with the HFHSD group, D-tagatose ameliorated these abnormalities: it significantly reduced fasting insulin (FINS) and the insulin resistance index (IRI), increased the insulin sensitivity index (ISI), lowered serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and elevated high-density lipoprotein cholesterol (HDL-C). D-Tagatose also mitigated oxidative stress and liver injury and attenuated systemic inflammation. D-Tagatose effectively prevented hepatic injury and visceral fat accumulation. Specifically, D-tagatose reshaped the gut microbial composition, promoting beneficial bacteria such as Lactobacillus, Bifidobacterium, and Lachnospiraceae_NK4A136_group while suppressing harmful bacteria including Alistipes and Colidextribacter. Metabolomic profiling further demonstrated that D-tagatose regulated key metabolites involved in amino acid and lipid metabolism pathways. Collectively, D-tagatose exerts its protective effects against HSHFD-induced metabolic disorders through the gut microbiota-metabolism axis, highlighting its potential as a functional food ingredient for the prevention and improvement of obesity-associated metabolic diseases.
Cordyceps militaris is an edible medicinal fungus with potential metabolic benefits, but its effects on type 2 diabetes mellitus accompanied by hyperlipidaemia (T2DM-HLP) remain incompletely understood. This study evaluated the effects of orally administered C. militaris ethanol extract (EAE; 2.0 g kg-1) and cordycepin (50 or 100 mg kg-1) in a T2DM-HLP mouse model over 6 weeks. Metabolic indices, serum transaminases, colon and liver histology, gut bacterial and fungal communities, serum metabolites, and FXR/TGR5-related molecular markers were assessed. Compared with the model group, EAE and 50 mg kg-1 cordycepin reduced serum lipid and transaminase levels to varying degrees and were associated with downward shifts in fasting blood glucose and oral glucose tolerance test curves. Histological alterations in the colon and liver were also less apparent in these two groups. Faecal 16S rDNA and ITS sequencing showed changes in the bacterial and fungal community structure, while untargeted serum metabolomics identified distinct metabolic profiles involving bile acids, fatty acids, amino acids, nucleotides, and redox-related metabolites. Enrichment analyses implicated bile secretion, primary bile acid biosynthesis, cholesterol metabolism, cAMP signalling, and amino acid metabolism. These changes were accompanied by increased colonic TGR5 and hepatic FXR immunoreactivity, increased hepatic Fxr, Nr0b2, and Ppara expression, and reduced Cyp7a1 expression. Responses to 100 mg kg-1 cordycepin were less consistent, indicating no simple dose-dependent relationship under the present conditions. Overall, EAE and cordycepin were associated with improved metabolic status and coordinated changes in the gut microbial composition, serum metabolism, and bile acid-related molecular readouts.
Objective: To identify research hotspots in natural products for obesity and compare their relative efficacy in preclinical models. Methods: Bibliometric analysis was performed using CiteSpace and Bibliometrix on publications from...
Rosmarinic acid (RA) significantly alleviates DSS-induced colitis by repairing the damaged colonic mucus barrier and reversing gut microbiota dysbiosis. However, it remains unclear whether the gut microbiota is required for this protective effect. To address this, pseudo-germ-free mouse models and fecal microbiota transplantation (FMT) were used to evaluate whether the gut microbiota is required for RA to restore mucus barrier integrity and alleviate colitis. The study showed that transplanting fecal microbiota from RA-pretreated donor mice into pseudo-germ-free recipients with colitis markedly alleviated colitic pathology. This was reflected by an 52% reduction in the disease activity index (DAI) score, improved histological scores, markedly lower serum pro-inflammatory cytokines (IL-6 and TNF-α), and upregulated mRNA expression of anti-inflammatory cytokines (IL-10 and IL-25). Moreover, the mucus barrier was substantially restored in recipient mice: goblet cell numbers increased approximately 5-fold (RH-FMT (recipient mice were transplanted with microbiota derived from the high-dose RA treatment group) vs. DSS group), mucus coverage rose from 5.24% (DSS) to 35.4% (RHF), and mRNA levels of tight junction proteins and mucins (e.g., ZO-1, MUC1) were elevated. Short-chain fatty acid (SCFA) levels recovered, with total SCFAs increasing by about 130.77%. Meanwhile, the gut microbiota of recipient mice was remodeled: beneficial bacteria such as Akkermansia and Limosilactobacillus increased, while harmful bacteria like Proteobacteria and Klebsiella decreased. However, direct oral administration of RA (at either high or low doses) to pseudo-germ-free mice did not produce these protective effects. Further correlation analysis revealed that the abundance of SCFA-producing beneficial genera-including Akkermansia, Limosilactobacillus, and Blautia_A-in recipient mice was significantly positively correlated with the expression of genes involved in the mucus barrier and tight junctions, as well as with SCFA levels. Thus, RA alleviates colitis through mucus barrier repair and modulation of SCFAs metabolism, a process that critically depends on the gut microbiota.
Biological rhythms allow mammals to adapt to environmental light-dark cycles, with photoperiod being a key modulator of metabolism and behavior, influencing body weight, and hepatic lipid metabolism in a sex-dependent manner. In this context, fruit (poly)phenols have been shown to regulate lipid metabolism, improving dyslipidemia in obese rats. Importantly, the metabolic effects of fruits rich in (poly)phenols are strongly influenced by the season of the fruits and the photoperiod. In this study, we evaluated the impact of sex and photoperiod and their interaction on the effects of two mixtures of seasonal fruit extracts enriched with (poly)phenols on hepatic lipid metabolism in obese rats. To this end, a summer mixture (SM; plum and cherry) and a winter mixture (WM; grape and pomegranate) were chronically administered to male and female Fischer 344 rats exposed to short (L6; 6 h light per day) or long (L18; 18 h light per day) photoperiods. Both SM and WM influenced the plasma lipid profile and hepatic expression of genes related to lipogenesis, β-oxidation, and fatty acid transport in a photoperiod- and sex-dependent manner. In male rats, the effects of the SM, characterized by a high content of anthocyanins and hydrolysable tannins, were strongly dependent on the photoperiod. Under L18 conditions, which mimic the fruits' growing season, the SM improved lipid handling and reduced hepatic Ppar-α expression, whereas under L6 conditions, it increased total hepatic cholesterol. Overall, these findings highlight that the bioactivity of dietary (poly)phenols is modulated by temporal and biological factors such as sex and photoperiod, providing new insights into chrononutrition and the development of personalized nutritional strategies to improve metabolic health.
The microbiota-gut-joint axis influences systematic and local inflammation via the gut microbiota. Our previous investigations have revealed that hyaluronic acid (HA) with specific molecular weight (MW) affects the human gut microbiota in a simulated batch fermentation system. However, the structure-property relationships and mechanism by which HA alleviates rheumatoid arthritis (RA) by modulating the gut microbiota remain unexplored. In this study, collagen-induced arthritis (CIA) Wistar rats received HAs of different MWs (2 kDa, 300 kDa, 3000 kDa) by oral gavage. HAs MW-dependently improved osteochondral health and cartilage injury, characterized by alleviated foot swelling, enhanced motor capacity and reduced pro-inflammatory mediator levels. Muti-omics analysis of the gut microbiota and joint transcriptomic studies revealed that HAs regulate the gut microbial composition, interactions, phenotype and intestinal barrier functions. High-MW HA upregulated beneficial bacteria (i.e., Lactobacillus, Clostridium sensu stricto 1 and Turicibacter) and arginine and proline metabolism while inhibiting harmful bacteria (i.e., Desulfovibrio and the NK4A214 group) and ECM-receptor interactions. Furthermore, alleviation of RA symptoms and similar characteristics of the gut microbiota were observed in a pseudo-germ-free (PGF) rat model after fecal microbiota transplantation (FMT) from donors of the high-MW HA group. These findings proved that the gut microbiota mediates the anti-rheumatic effect of HAs on the microbiota-gut-joint axis, providing a new opportunity to understand the structure-property relationships in RA therapy.
Acute viral hepatitis is characterized by excessive inflammatory and antiviral immune responses that contribute to liver injury. Polyinosinic-polycytidylic acid [poly(I:C)], a synthetic analog of viral double-stranded RNA, is widely used to mimic virus-induced acute liver damage. Increasing evidence indicates that immunomodulatory probiotics (immunobiotics) can influence immune responses beyond the gut and exert beneficial effects in extraintestinal tissues like the liver. In this study, we evaluated the protective effects of Lactiplantibacillus plantarum CRL1506 and a surface-modified ΔdltD mutant strain in a murine model of poly(I:C)-induced acute liver injury. Oral administration of the wild-type CRL1506 strain significantly reduced serum transaminase levels and attenuated histopathological liver damage following a poly(I:C) challenge, whereas the mutant strain failed to confer protection. The protective effect induced by the CRL1506 strain was associated with a marked modulation of hepatic inflammatory mediators, including a reduction in proinflammatory cytokines, and improvements of antiviral factors and regulatory cytokines. This modulation of the liver cytokine profile was not achieved by the ΔdltD mutant strain, highlighting the role of lipoteichoic acid in the regulation of the immune system. Collectively, our findings demonstrate that L. plantarum CRL1506 confers protection against virus-like acute liver injury by fine-tuning inflammatory and antiviral immune pathways and highlight the relevance of bacterial surface configuration in mediating its immunobiotic and hepatoprotective effects. This study underlines the potential of immunobiotic strains as functional dietary interventions to mitigate acute liver inflammation triggered by viral components.
Prebiotic inulin improves obesity-related metabolic disturbances, yet its clinical efficacy shows marked interindividual heterogeneity. The key microbial players, interspecies interactions, and downstream effector pathways governing differential responsiveness remain poorly defined. This study is aimed at identifying functional bacteria driving response heterogeneity, delineating the underlying mechanisms, and establishing a predictive biomarker system. Humanized obese mice were generated by high-fat diet preconditioning, and donor-specific response differences were recapitulated by one-to-one fecal microbiota transplantation. Causal links were validated via multi-omics integration, in vitro co-culture, in vivo bacterial recolonization/clearance, and independent cohort verification. Response heterogeneity was driven by antagonism between Desulfovibrio desulfuricans and Roseburia intestinalis. H2S derived from D. desulfuricans directly suppressed R. intestinalis growth and butyrate production, and this microbial interaction axis was functionally relevant to the heterogeneous metabolic responses to inulin. An inulin response index (IRI) based on the Roseburia-to-Desulfovibrio abundance ratio prospectively predicted responder phenotypes. D. desulfuricans gavage markedly attenuated inulin benefits in high-responder microbiota-colonized mice, while sodium molybdate-mediated H2S inhibition, R. intestinalis or sodium butyrate supplementation restored metabolic benefits in low-responder microbiota-colonized mice. Butyrate conferred protection by strengthening gut barrier function, activating GLP-1/PYY secretion, and suppressing adipose inflammation. We uncover a novel D. desulfuricans-H2S-R. intestinalis-butyrate antagonistic axis that mechanistically explains inulin response heterogeneity, providing a mechanistic rationale for personalized nutrition and supporting a clinically translatable predictive index and targeted intervention strategy.
γ-Aminobutyric acid (GABA)-rich fermented rice bran (GFRB) is a multi-component fermented food matrix with potential metabolic benefits, but its effects on high-fat diet (HFD)-induced liver injury and associated gut microbial and metabolic changes remain unclear. In this study, we characterized the metabolite profile of GFRB and evaluated its effects in rats with HFD-induced liver injury. Male Sprague-Dawley rats were fed a control diet or HFD with or without GABA or low- or high-dose GFRB supplementation for 12 weeks. Gut microbiota, fecal short-chain fatty acids, and fecal metabolomic profiles were further analyzed as exploratory outcomes. GFRB contained markedly increased GABA and was enriched in amino acid- and fermentation-related metabolites, including glutamine, ornithine, citrulline, lactate, and succinate. HFD feeding induced a relatively mild non-alcoholic fatty liver disease-like phenotype characterized by hepatic histopathological alterations, including fatty changes and inflammation. GFRB supplementation attenuated these hepatic alterations, as reflected by a reduced NAFLD activity score in the low-dose GFRB group and decreased hepatic interleukin-6 levels in the high-dose GFRB group. Exploratory analyses also identified alterations in gut microbiota composition and fecal metabolite profiles, particularly in amino acid- and nitrogen-related metabolic pathways. Overall, these findings suggest that GFRB may attenuate early HFD-induced liver injury, potentially through modulation of hepatic inflammation. The accompanying gut microbiota and metabolomic changes should be considered exploratory observations that warrant further mechanistic investigation.
Immune homeostasis serves as the foundation for disease prevention and the cornerstone for ensuring human health. The effects of Abelmoschus manihot (L.) leaf flavonoids (AMLF) on restoring immune function were investigated in a cyclophosphamide (CTX)-induced immunosuppressed mouse model. The underlying repair mechanisms were explored by an integrative analysis of intestinal microbiomics and serum metabolomics. The results demonstrated that AMLF markedly elevated the spleen and thymus indices, promoted the proliferation of splenic lymphocytes in the presence of concanavalin A (ConA) or lipopolysaccharide (LPS) and CD4+ and CD8+ T lymphocyte subsets, and concomitantly enhanced the serum levels of key immunomodulatory cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α), and the antibody immunoglobulin G (IgG). In addition, AMLF treatment effectively mitigated CTX-induced histopathological injuries to immune organs and the colon. AMLF were also found to protect the liver by regulating antioxidant enzyme activities. Furthermore, AMLF markedly improved the intestinal microbial community structure, promoted the enrichment of beneficial bacteria (Lactobacillaceae and Prevotellaceae), inhibited pathogenic bacteria (Muribaculaceae and Desulfovibrionaceae), and increased the content of short-chain fatty acids (SCFAs). Serum metabolomic analysis showed that AMLF upregulated the levels of leukotrienes, S-(PGA1)-glutathione and prostaglandin E2. Correlation analysis identified g_Alistipes, g_norank_f_Muribaculaceae, and g_Kurthia as potential microbiota strongly associated with the restoration of immune and metabolic homeostasis after AMLF treatment. These findings support the dual potential of AMLF in functional foods and as immunomodulatory adjuvants.
Postmenopausal osteoporosis, characterized by estrogen deficiency, leads to significant bone loss and an elevated risk of fracture. While Agrocybe chaxingu is an edible mushroom with recognized health benefits, its therapeutic potential and underlying mechanisms in treating osteoporosis remain largely unexplored. This study aimed to investigate the anti-osteoporotic effects of Agrocybe chaxingu extracts (ACPE) and elucidate their potential mechanism of action. An ovariectomized (OVX) rat model was employed to mimic postmenopausal osteoporosis. ACPE treatment significantly ameliorated OVX-induced bone loss, as evidenced by increased bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and decreased trabecular separation (Tb.Sp). ACPE administration effectively improved the OVX-induced increase in serum ALP and decline in serum phosphorus levels. Mechanistically, ACPE restores dysbiosis caused by OVX, enriches beneficial bacteria such as Lactobacillus, and increases the abundance of phosphorus transport-related bacterial communities, including g_Corynebacterium and g_DA101, while upregulating the expression of Pit1 and Pit2, suggesting a potential involvement in improved phosphorus homeostasis, thereby improving osteoporosis. This study demonstrates the efficacy of ACPE in improving osteoporosis, providing a theoretical basis for its use as a nutritional supplement for postmenopausal osteoporosis.
Anthocyanins, naturally occurring pigments in fruits and vegetables, have gained attention for their potential health benefits, including anti-inflammatory and gut-protective properties. In this study, we investigated the protective effects and underlying mechanisms of cyanidin-3-O-glucoside (C3G), a major dietary anthocyanin, in a dextran sulfate sodium (DSS)-induced murine model of inflammatory bowel disease (IBD). Oral administration of C3G significantly alleviated disease activity, attenuated body weight loss, reduced colon shortening, and suppressed systemic and colonic inflammation. C3G treatment restored intestinal barrier integrity by upregulating mucin 2 (MUC2) and key tight junction proteins, including occludin, claudin-1, and ZO-1. Integrated transcriptomic and network pharmacology analyses identified the PI3K-Akt signaling pathway and apoptosis as key targets of C3G. Experimental validation showed that C3G reduced TUNEL-positive cells in the colon and modulated apoptosis-related proteins by increasing Bcl-2 expression and decreasing cleaved caspase-3 levels. These findings indicate that C3G ameliorates experimental colitis, potentially through modulation of the PI3K-Akt pathway and suppression of epithelial apoptosis, supporting its potential as a functional food component for intestinal health.
Upper respiratory tract infections (URTIs) are common viral illnesses whose burden increases with age-related declines in innate immunity. Maitake mushrooms (Grifola frondosa) have immunomodulatory properties, but evidence in healthy humans, particularly regarding age-related innate immune responses, remains limited. In this randomized, double-blind, placebo-controlled trial, healthy young adults (18-20 years) and middle-aged/older adults (40-85 years) consumed bread containing one of two maitake strains (Y10M or C5304) or a placebo daily for 11 weeks (young adults) or 18 weeks (middle-aged/older adults). While the overall incidence of URTI episodes did not differ between groups, symptom-specific analyses suggested strain-dependent differences. Y10M supplementation was associated with fewer cumulative days of fever and runny nose in both age groups and with sore throat in young adults, whereas C5304 showed limited effects. Notably, Y10M was associated with changes in innate immune parameters in middle-aged/older adults, including increased plasmacytoid dendritic cell frequency, activation of conventional dendritic cells, and upregulation of type I interferon-related gene expression and IL12A following ex vivo stimulation. These findings suggest that dietary maitake supplementation, particularly with the Y10M strain, may reduce the cumulative burden of selected URTI-related symptoms and modulate antiviral innate immune responses in healthy adults, with effects that may differ by strain and age cohort.
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by involuntary motor and vocal tics. Emerging evidence suggests that microRNA (miRNA) regulation and the gut-brain axis (GBA) may contribute to TS pathophysiology. Lactiplantibacillus plantarum PS128 (PS128) is a well-studied psychobiotic strain known to influence brain function through neurotransmitter modulation. This double-blind, randomized, placebo-controlled trial investigated the efficacy of a 12-week PS128 intervention on clinical symptoms-including tic severity, attention, and gastrointestinal discomfort-alongside circulating miRNA expression and gut microbiota composition in children aged 4-18 years with TS. Clinical outcomes were assessed using the Yale Global Tic Severity Scale (YGTSS), Clinical Global Impression (CGI), Visual Analogue Scale of Gastrointestinal Discomfort (VAS-GI), Continuous Performance Test (CPT), and neuropsychological assessments. Blood-based miRNA profiling and fecal microbiota analyses were conducted to explore potential mechanisms. Seventy-three participants completed the study. Improvements in YGTSS, CGI, and neuropsychological outcomes were comparable between groups. The primary endpoint, reduction in YGTSS score, did not differ significantly between groups. However, the PS128 group exhibited significantly greater reductions in gastrointestinal symptoms, particularly upper abdominal pain, and showed a trend toward improved attentional performance on the CPT. miRNA sequencing identified eight differentially expressed miRNAs following PS128 intervention, which were predicted to be involved in nervous system development and synaptic regulation. The qRT-PCR validation confirmed significant upregulation of miR-199a-3p and miR-143-3p in the PS128 group compared with placebo. Fecal microbiota analysis revealed increased Lactiplantibacillus abundance after PS128 intervention, which positively correlated with miR-199a-3p expression and negatively correlated with CGI scores. No intervention-related adverse events were reported. Despite no significant effect on core tic severity, PS128 improved gastrointestinal and attentional symptoms with accompanying GBA molecular changes, supporting further investigation as an adjunctive therapy for pediatric TS.
Dry eye disease is associated with tear film instability and ocular discomfort, which may be exacerbated by prolonged visual display terminal (VDT) exposure. This 12-week randomized, double-blind, placebo-controlled trial enrolled 100 adults with dry eye symptoms and ocular fatigue, randomly assigned 1 : 1 to oral supplementation with standardized small black soybean extract (SSBS) or matched placebo. The primary efficacy endpoint was tear film break-up time (TBUT); secondary endpoints included the Ocular Surface Disease Index (OSDI) score, visual analogue scale (VAS) scores, and objective ocular surface parameters. In the per-protocol set (n = 81), SSBS supplementation produced a significantly greater improvement in TBUT than placebo at Week 12 (+0.35 ± 1.54 vs. -0.33 ± 1.46 s; p = 0.0457; ANCOVA p = 0.0397). SSBS also produced a significantly greater reduction in OSDI total score compared with placebo (-22.41 ± 23.16 vs. -12.65 ± 14.59; p = 0.0252; ANCOVA p = 0.0359), with significant improvement in the ocular symptoms subscale. Exploratory subgroup analyses suggested greater symptom improvement in subjects with severe baseline symptoms and favorable changes in tear secretion and conjunctival hyperemia in subjects with high digital device exposure. No clinically meaningful safety concerns were identified. The between-group difference in TBUT was modest and the subgroup analyses were exploratory; accordingly, these results indicate a consistent signal that SSBS supplementation may support tear film stability and alleviate dry eye-related symptoms.
Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide. Extensive research into preventive nutritional strategies against CVD is needed. This meta-analysis aims to systematically evaluate the effects of flavonoid-rich...
Nutrigenomics explores how nutrients interact with the genome to influence metabolic and physiological functions through microbial and molecular mechanisms. Nutrients and bioactive food compounds act as biochemical modulators that regulate...
Metabolic dysfunction-associated steatotic liver disease (MASLD) primarily results from excessive nutrient consumption, with lifestyle modifications, particularly dietary interventions, constituting a principal strategy for its management. This study sought to examine the ameliorative effects of a quinoa diet (QD) on hepatic lipid metabolism in mice with MASLD. Six-week-old male C57BL/6J mice were fed with a QD for 12 weeks, and age-matched male mice were subjected to a high-fat diet (HFD) to establish obese MASLD models, followed by QD intervention. Compared with the chow diet (CD) group, QD supplementation maintained lower levels of Lee's index, serum AST and ALT, confirming its regulatory effect on hepatic fat accumulation. In MASLD mice, QD supplementation markedly decreased Lee's index, blood glucose, ALT, AST, LDL-C, TC and TG contents. It also downregulated the gene expression of ACC, FAS and SCD-1 as well as the protein levels of PPARγ and PLIN2, thereby alleviating HFD-triggered hepatic lipid metabolism disorders. Lipids and lipid-like molecules were the most significantly altered metabolites in QD-treated mice, accounting for 50.87% of all differential metabolites. Collectively, quinoa demonstrates the capacity to enhance hepatic lipid metabolism in mice with metabolic-associated steatotic liver disease (MASLD), with the PPARγ-PLIN2 signaling pathway potentially serving as a central therapeutic target. These findings indicate that quinoa holds significant promise as a functional food for the intervention and mitigation of MASLD.
