Journal of Nutritional Biochemistry最新文献

{"title":"Naringenin alleviates heat stress-induced liver injury in Ningdu yellow chickens by decreasing RIPK3 and PDC binding","authors":"Zhenni Liu ,&nbsp;Ruoyun Tang ,&nbsp;Qiurong Qi,&nbsp;Siting Lin,&nbsp;Ping Liu,&nbsp;Gaofeng Cai,&nbsp;Zhanhong Zheng,&nbsp;Xiaoquan Guo,&nbsp;Xiaona Gao","doi":"10.1016/j.jnutbio.2025.109894","DOIUrl":"10.1016/j.jnutbio.2025.109894","url":null,"abstract":"<div><div>Naringenin, a flavonoid extract, possesses anti-inflammatory, antioxidant, hepatoprotective, antitumor, and antineurotoxic properties. This study investigated the antiheat stress effects in broilers by adding 200mg/kg naringenin to the diet of Ningdu yellow chicken under heat stress conditions. Heat stress conditions was controlled at 37±2°C (7:00 a.m.–7:00 p.m.) and 24±2°C (7:00 p.m.–7:00 a.m.) at humidity maintained at 60–65%. The results suggest that naringenin elevated the body weight and the ratio of liver mass to weight of Ningdu yellow chicken significantly. Additionally, naringenin significantly reduces heat stress level, improves liver function and antioxidant capacity. Meanwhile, the levels of necroptosis indexes (CYLD, RIPK1, RIPK3 and MLKL) and oxidative stress indexes (PDC, PYGL, GLUL and GLUD1) are downregulated by naringenin. Naringenin mitigated liver damage by decreasing inflammatory indexes caused by heat stress, including NF-κB, IL-1β, IL-18 and HMGB1. This anti-inflammatory effect arose through the downlink binding of the necroptosis index (RIPK3) and the oxidative stress index (PDC) as shown in results of fluorescence co-localization and co-immunoprecipitation. The use of naringenin in poultry may be a possible feed additive to address clinical heat stress.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109894"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-restricted feeding mitigates HFD-induced sarcopenic obesity in aging mice through improving the sensitivity of FGF21","authors":"Ting Wang ,&nbsp;Hongkun Lin ,&nbsp;Yan Deng ,&nbsp;Wenwen Chen ,&nbsp;Yangliu Xu ,&nbsp;Li Wang ,&nbsp;Aojia Zhou ,&nbsp;Yidan Zhang ,&nbsp;Ziping Wang ,&nbsp;Xin Jin ,&nbsp;Li Zhang ,&nbsp;Xin Wang ,&nbsp;Yang Zhou ,&nbsp;Ruhan Wang ,&nbsp;Shuang Rong","doi":"10.1016/j.jnutbio.2025.109893","DOIUrl":"10.1016/j.jnutbio.2025.109893","url":null,"abstract":"<div><div>Time-restricted feeding (TRF) is a dietary intervention that has been shown to have numerous health benefits. However, it is important to further investigate the potential effectiveness of TRF in addressing sarcopenic obesity (SO), which is characterized by a combination of age-related obesity and sarcopenia. In this study, 14-month-old C57BL/6J male mice were fed either regular chow diet or high-fat diet (HFD), and had either ad libitum or restricted access to food for 8 hours daily (Intervention for 7 months). For the human trial (ChiCTR2100052876), obese individuals (<em>n</em>=21) with a Body Mass Index ≥28 were recruited and instructed to adopt an 8-hour eating window and a 16-hour fasting period. Here, we found that the TRF intervention significantly reduced global fat mass (<em>P</em> &lt; .001) and volume (<em>P</em> &lt; .05), and increase lean mass compared to mice fed with HFD. Furthermore, TRF improved overall metabolic mobility (8h TRF+HFD vs. AL+HFD). This intervention also enhanced liver FGF21 protein levels (<em>P</em> &lt; .01) and the expression of FGFR1 and FGF21 target genes in adipose and muscle tissues, thus improving mitochondrial quality control in these tissues. Notably, TRF interventions led to a significant decrease in serum FGF21 levels (<em>P</em> &lt; .05). In the human trial, TRF intervention resulted in a significant reduction in weight (<em>P</em> &lt; .001) and body fat levels (<em>P</em> &lt; .001) among obese individuals, as well as a decrease in serum GLU (<em>P</em> &lt; .001), insulin (<em>P</em> &lt; .001), and TC levels (<em>P</em> &lt; .05). Overall, the findings indicate that TRF intervention improves SO by regulating liver FGF21 expression, thereby enhancing FGF21 sensitivity in adipose and muscle tissues.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109893"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased circulating apolipoprotein Cs are implicated in the association between elevated serum retinol and retinol-binding protein 4 and adverse progression of metabolic syndrome in adults: A prospective study","authors":"Danyu Chen ,&nbsp;Keliang Xie ,&nbsp;Chang Gao ,&nbsp;Yingdi Yang ,&nbsp;Ying Xu ,&nbsp;Bang-yan Li ,&nbsp;Yue Xi ,&nbsp;Ju-Sheng Zheng ,&nbsp;Yu-ming Chen","doi":"10.1016/j.jnutbio.2025.109892","DOIUrl":"10.1016/j.jnutbio.2025.109892","url":null,"abstract":"<div><div>Prior research has highlighted the significant roles of circulating retinol, retinol-binding protein 4 (RBP4), and apolipoprotein C (ApoC) in metabolic health. This study investigates the joint association of retinol and RBP4 with metabolic syndrome (MetS) and examines the potential mediating role of ApoCs in these relationships. This prospective study included 3,009 and 2,724 participants with baseline serum retinol and RBP4 data, respectively. Over a 9-year follow-up among 2,621 participants, 1,136, 127, 696, and 662 were categorized into MetS-free, recovered, incident MetS, and persistent MetS groups, respectively. Midway through the study, ApoC1-4 levels were measured in 2316 participants. Adjusted odds ratios (95% CIs) for the highest (vs. lowest) tertile of retinol and RBP4 levels were 3.63 (2.69–4.92) and 5.64 (4.05–7.92) for 9-year persistent MetS, respectively. The corresponding hazard ratios (95% CIs) were 1.67 (1.39–2.01) and 1.67(1.38, 2.03) for incident MetS, and 0.65 (0.41–1.03) and 0.44 (0.28, 0.70) for recovered MetS (all <em>P</em>-trends&lt;.05). A synergistic association of retinol and RBP4 with MetS risk was observed for persistent MetS. Higher levels of retinol or RBP4 were associated with increased concentrations of ApoC1-4, which were linked to a greater risk of incident and persistent MetS. A newly developed composite score (ApoCS), derived from ApoC1-4 levels, explained 30.5% and 24.5% of the association between retinol or RBP4 and MetS, with ApoC2 and ApoC3 contributing predominantly to this connection. Our study identified notable positive correlations between serum retinol and RBP4 levels and MetS progression, explained by increases in circulating ApoC2 and ApoC3 within a Chinese cohort.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109892"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal omega-3 polyunsaturated fatty acids improved levels of DHA-enriched phosphatidylethanolamines and enriched lipid clustering in the neuronal membranes of C57BL/6 mice fetal brains during gestation","authors":"Innocent Uzochukwu Okagu ,&nbsp;Olatunji Anthony Akerele ,&nbsp;Tiffany Fillier ,&nbsp;Thu Huong Pham ,&nbsp;Raymond Thomas ,&nbsp;Katie A. Wilson ,&nbsp;Sukhinder Kaur Cheema","doi":"10.1016/j.jnutbio.2025.109891","DOIUrl":"10.1016/j.jnutbio.2025.109891","url":null,"abstract":"<div><div>The composition of brain lipids is crucial for neurodevelopment and brain function. Diets enriched in omega (n)-3 polyunsaturated fatty acids (PUFA) can modulate brain lipid composition. However, the influence of maternal n-3 PUFA intake on fetal brain lipidome and neuronal membrane structure during gestation is not well studied. Eight-week-old female C57BL/6 mice were fed low or high n-3 PUFA semi-purified diets for two weeks before mating and during gestation. Fetal brain lipidome and neuronal membrane structure were studied at gestation day (GD) 12.5 (mid) and 18.5 (late) using liquid chromatography high-resolution accurate mass tandem mass spectrometry and computational techniques. Maternal diets high in n-3 PUFA increased fetal brain total phosphoethanolamine, phosphoinositol, phosphoglycerol, and phosphoserine glycerophospholipids, compared to the low n-3 PUFA diet. Docosahexaenoic acid (DHA, 22:6n-3)-enriched phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and lyso-PC (LPC) fatty acyl species increased as gestation progressed in the high n-3 PUFA group, compared to low n-3 PUFA. These fatty acyl species and phospholipids promote neurotransmission, memory, and cognition. A high n-3 PUFA diet increased the area per lipid in fetal neuronal membranes as gestation progressed, indicating improved membrane fluidity. Furthermore, a high n-3 PUFA diet increased the clustering of membrane lipids associated with neurotransmission, memory, and cognition (ceramide, PE, and cholesteryl ester) as gestation progressed. Our findings show for the first time that maternal diets high in n-3 PUFA before and during gestation improve fetal brain lipidome and membrane area per lipid that may enhance brain development and function.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109891"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspartame consumption linked to delayed puberty and mitochondrial Dysfunction: Evidence from human and animal studies","authors":"Yang-Ching Chen ,&nbsp;Zih Ling Wang ,&nbsp;Yu-Fang Lin ,&nbsp;Chia-Yuan Lin ,&nbsp;Shih-Yuan Hsu ,&nbsp;Jacus S. Nacis ,&nbsp;Rong-Hong Hsieh","doi":"10.1016/j.jnutbio.2025.109889","DOIUrl":"10.1016/j.jnutbio.2025.109889","url":null,"abstract":"<div><div>This study investigates the impact of aspartame consumption on pubertal timing in females. The research employs both human and rat models to explore underlying mechanisms. In the Taiwan Pubertal Longitudinal Study (2018–2022), 858 girls aged 6–12 were assessed for aspartame intake and puberty outcomes. Concurrently, female Sprague Dawley rats were exposed to low (30 mg/kg) or high (60 mg/kg) doses of aspartame from prenatal to postnatal stages. Results demonstrate that aspartame disrupts the hypothalamic–pituitary–gonadal (HPG) axis in rats, causing mitochondrial dysfunction and reduced ovarian mitochondrial biogenesis, leading to delayed puberty. Human data indicates higher aspartame consumption correlates with a decreased risk of precocious puberty (odds ratio = 0.63, 95% confidence interval = 0.42–0.96; <em>p</em> for trend = 0.03). These findings suggest long-term aspartame consumption may delay puberty, necessitating further research to inform dietary guidelines, especially for vulnerable populations such as prepubertal girls.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109889"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to bisphenol A and sodium nitrate found in processed meat induces endocrine disruption and dyslipidemia through PI3K/AKT/SREBP pathway in zebrafish larvae","authors":"Santosh Pushpa Ramya Ranjan Nayak ,&nbsp;Anamika Das ,&nbsp;Karthikeyan Ramamurthy ,&nbsp;Mukesh Pasupuleti ,&nbsp;Rajakrishnan Rajagopal ,&nbsp;Jesu Arockiaraj","doi":"10.1016/j.jnutbio.2025.109887","DOIUrl":"10.1016/j.jnutbio.2025.109887","url":null,"abstract":"<div><div>Meat is a staple in many cultural diets, and the consumption of processed meats has increased significantly worldwide. The widespread use of sodium nitrate (NaNO₃) as a preservative and the unintentional leaching of bisphenol A (BPA) from packaging into meats have raised health concerns. This study evaluates the combined toxicity of BPA and NaNO₃ despite their individual safety assessments. Our findings reveal that coexposure to BPA and NaNO₃ at levels found in processed meats induces mortality and malformations in zebrafish larvae. The combined exposure triggers oxidative stress, lipid peroxidation, dyslipidemia, inflammation, and apoptosis. Network toxicology analysis elucidates the molecular mechanisms underlying metabolic dysfunction caused by these substances. Dysregulation of genes related to thyroid function (<em>tsh-β, dio-1, thr-b</em>) and inflammation (<em>tnf-α, il-1β, il-6, nfκb</em>) was observed in the co-exposure group. Additionally, this group exhibited increased lipid accumulation, elevated cholesterol and triglyceride levels, and dysregulation of essential lipid metabolism genes (<em>srebp2, pcsk9</em>). Co-exposure also impaired larval motility and behavior, evidenced by hypolocomotion and reduced acetylcholinesterase levels. Further gene expression analysis showed increased levels of <em>pi3k</em> and <em>akt,</em> two major signaling molecules. Ultimately, the simultaneous exposure to BPA and NaNO₃ leads to disruptions in the endocrine system and abnormal lipid levels via activating the PI3K/AKT/SREBP pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109887"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diosgenin alleviates lipid accumulation in NAFLD through the pathways of ferroptosis defensive and executive system","authors":"Linya Wang ,&nbsp;Hongzhuan Yu ,&nbsp;Dongxian Wang ,&nbsp;Guoliang Yin ,&nbsp;Suwen Chen ,&nbsp;Xin Zhang ,&nbsp;Wenfei Yu ,&nbsp;Decheng Meng ,&nbsp;Hongshuai Liu ,&nbsp;Wenying Jiang ,&nbsp;Fengxia Zhang","doi":"10.1016/j.jnutbio.2025.109886","DOIUrl":"10.1016/j.jnutbio.2025.109886","url":null,"abstract":"<div><div>The most prevalent liver condition globally is non-alcoholic fatty liver disease (NAFLD), for which no approved therapies currently exist. Diosgenin, an important component in plants from the <em>Leguminosae, Dioscoreaceae</em>, and <em>Solanaceae</em> families, has demonstrated considerable anti-inflammatory and antioxidant effects. Nonetheless, the specific mechanism by which it may act in managing NAFLD remains unclear. Our research aims to explore the effects and molecular mechanisms of DG on NAFLD by utilizing both in vivo and in vitro experimental approaches. To investigate the effect of DG on hepatic steatosis, we used Sprague-Dawley rats induced by a high-fat diet (HFD) and HepG2 cells exposed to free fatty acids. Oil red O staining and hematoxylin-eosin (H&amp;E) staining were used to explore lipid accumulation and hepatic degeneration. ROS staining, SOD, MDA, and Fe²⁺kits were used to detect the indexes related to oxidative stress in ferroptosis in hepatic tissues and cells. IFSP1 and pcDNA3.1-ACSL4 plasmid were used to knock down Ferroptosis suppressor protein1 (FSP1) and promote the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) in HepG2 cells. DG improved lipid metabolism disorders and liver damage induced by a high-fat diet in rats with NAFLD. Furthermore, the administration of DG notably decreased oxidative stress levels and liver Fe²⁺ concentrations in rats. Additionally, in vitro experiments demonstrated that DG treatment markedly attenuated ferroptosis and ROS accumulation in HepG2 cells induced by FFAs. Moreover, overexpression of hepatic ACSL4 expression by pcDNA3.1-ACSL4 plasmid promoted the regulatory effects of DG on LPCAT3 and ALOX15. Our research shows that DG can alleviate NAFLD by regulating the FSP1/COQ10 pathway of the ferroptosis defense system and the ACSL4/LPCAT3/ALOX15 pathway of the ferroptosis execution system. Therefore, DG may serve as a novel inhibitor of ferroptosis for the treatment of NAFLD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109886"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg1 alleviated experimental colitis in obesity mice by regulating memory follicular T cells via Bcl-6/Blimp-1 pathway","authors":"Zeyun Zhang ,&nbsp;Jiaqi Huang ,&nbsp;Xiyan Zhu ,&nbsp;Bailin Deng ,&nbsp;Haimei Zhao ,&nbsp;Haiyan Wang ,&nbsp;Duanyong Liu","doi":"10.1016/j.jnutbio.2025.109880","DOIUrl":"10.1016/j.jnutbio.2025.109880","url":null,"abstract":"<div><div>The pathological mechanisms of ulcerative colitis (UC) are closely related with abnormal memory follicular helper T (mTfh) cell subsets and the Bcl-6/Blimp-1 signaling pathway. Ginsenoside Rg1 (G-Rg1) has been confirmed to exhibit therapeutic effects in obese mice with dextran sulfate sodium (DSS)-induced ulcerative colitis. The aim of this study was to investigate the mechanism of action of G-Rg1 in obese mice with UC by observing mTfh cell subsets and the Bcl-6/Blimp-1 signaling pathway. Obese mice with UC were treated with G-Rg1 at a dose of 200 mg/kg. Disease activity was assessed macroscopically and microscopically, and cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to analyze mTfh cell subsets, and Western blotting to assess protein expression related to the Bcl-6/Blimp-1 pathway. qPCR was used to detect the expression of Bcl-6/Blimp-1, and immunofluorescence was utilized to compare Bcl-6/Blimp-1 expression between different groups. G-Rg1 treatment ameliorated the symptoms of DSS-induced colitis, alleviated the pathological changes in the colonic tissue of obese mice with ulcerative colitis, and reduced the levels of inflammatory cytokines in these mice. Furthermore, flow cytometry analysis indicated that G-Rg1 modulated the balanceof mTfh cells subsets by increasing central memory Tfh (cmTfh) cells and decreasing effector memory Tfh (emTfh) cells, thereby mitigating ulcerative colitis in obese mice. qPCR results revealed the significant upregulation of Bcl-6 and the downregulation of Blimp-1 expression in the DSS group, which was effectively reversed by G-Rg1 treatment. These findings were further confirmed by Western blot and immunofluorescence assays. Collectively, the qPCR, Western blot, and immunofluorescence results demonstrated the pivotal role of the Bcl-6/Blimp-1 signaling pathway in the therapeutic process of G-Rg1 for ulcerative colitis in obese mice. Ginsenoside Rg1 alleviates experimental colitis in obese mice by modulating the proportion of mTfh cell subsets via the Bcl-6/Blimp-1 signaling pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109880"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-aminobutyric acid ameliorates diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) progression in mice via enhancing AMPK/SIRT1 pathway and modulating the gut-liver axis","authors":"Felicianna ,&nbsp;Emily Kwun Kwan Lo ,&nbsp;Congjia Chen ,&nbsp;Marsena Jasiel Ismaiah ,&nbsp;Fangfei Zhang ,&nbsp;Hoi Kit Matthew Leung ,&nbsp;Hani El-Nezami","doi":"10.1016/j.jnutbio.2025.109885","DOIUrl":"10.1016/j.jnutbio.2025.109885","url":null,"abstract":"<div><div>Alpha-aminobutyric acid (ABA) is a nonproteinogenic amino acid, a metabolite which could be generated from the metabolism of methionine, threonine, serine and glycine or as a gut-microbiome-derived metabolite. Changes in ABA levels have been embroiled in metabolic dysfunction-associated steatotic liver disease (MASLD) intervention studies, but their relation to MASLD pathogenesis remains unclear. Hence, this present study aimed to investigate the effect of oral ABA supplementation on the progression of a high fat/high cholesterol diet (HFD) induced MASLD mice model. ABA was found to remodel the gut microbiome composition and ameliorate MASLD parameters in HFD-fed mice. ABA mitigated HFD-induced gain in liver weight, hepatic steatosis, insulin resistance, serum and hepatic triglyceride levels, and liver cholesterol levels. Modulation of lipid metabolism was observed in the liver, in which expression of proteins and/or genes involved in <em>de novo</em> lipogenesis were suppressed, while those involved in fatty acid oxidation and autophagy were upregulated together with cellular antioxidant capacity, in addition to the enhancement of the AMPK/SIRT1 pathway. ABA reshaped the gut composition by enriching nine bacterial species, including <em>Helicobacter hepaticus, Desulfovibrio sp. G11, Parabacteroides distasonis</em>, and <em>Bacteroides fragilis</em>, while diminishing the abundance of 16 species, which included four <em>Helicobacter</em> species. KEGG pathway analysis of microbial functions found that ABA impeded secondary bile acid biosynthesis – which was reflected in the faecal BA composition analysis. Notably, ABA also inhibited ileal FXR-Fgf15 signaling, allowing for increased hepatic Cyp7a1 expression to eliminate cholesterol buildup in the liver. Overall, our findings indicate that ABA could be used as a promising therapeutic approach for the intervention of MASLD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109885"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA hypermethylation-induced suppression of ALKBH5 is required for folic acid to alleviate hepatic lipid deposition by enhancing autophagy in an ATG12-dependent manner","authors":"Chaoqun Huang ,&nbsp;Yaojun Luo ,&nbsp;Youhua Liu ,&nbsp;Jiaqi Liu ,&nbsp;Yushi Chen ,&nbsp;Botao Zeng ,&nbsp;Xing Liao ,&nbsp;Yuxi Liu ,&nbsp;Xinxia Wang","doi":"10.1016/j.jnutbio.2025.109870","DOIUrl":"10.1016/j.jnutbio.2025.109870","url":null,"abstract":"<div><div>Nonalcoholic fatty liver disease (NAFLD) occurs when too much fat builds up in the liver. As a growing worldwide epidemic, NAFLD is strongly linked with multiple metabolic diseases including obesity, insulin resistance, and dyslipidemia. However, very few effective treatments are currently available. Folate, an essential B-group vitamin with important biological functions including DNA and RNA methylation regulation, has been shown to have a protective effect against NAFLD with its underlying mechanism remains largely unclear. Here, we show that administration of folic acid significantly improves glucose tolerance, insulin sensitivity, and dyslipidemia in high-fat diet (HFD) fed mice. Moreover, folic acid treatment significantly inhibits lipid deposition in hepatocytes both <em>in vivo</em> and <em>in vitro</em>. Mechanically, folic acid reduces the expression of m⁶A demethylase AlkB homolog 5 (ALKHB5) via promoter DNA hypermethylation. Decreased ALKBH5 causes increased m⁶A modification and increased expression of ATG12 in a demethylase activity-dependent manner, thereby promoting autophagy and preventing hepatic steatosis. Inhibition of ATG12 induced by overexpression of ALKBH5 could impair autophagy and the inhibitory effect of folic acid on lipid accumulation in hepatocytes. Together, these findings provide novel insights into understanding the protective role of folic acid in the treatment of NAFLD and suggest that folic acid may be a potential agent for combating NAFLD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"140 ","pages":"Article 109870"},"PeriodicalIF":4.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}