Journal of Nutritional Biochemistry最新文献

{"title":"Enhancing Wound Healing via Modulation of Autophagy-Induced Apoptosis: The Role of Nicotinamide Riboside and Resveratrol in Streptozotocin-Treated Diabetic Rat.","authors":"Morvarid Siri, Mohammad Hasan Maleki, Seyed Mohammadmahdi Meybodi, Seyed Amirhossein Mazhari, Fatemeh Ghaderi Saviri, Amirreza Dehghanian, Maryam Naseh, Nafiseh Esmaeili, Sanaz Dastghaib, Zeinab Aryanian","doi":"10.1016/j.jnutbio.2024.109811","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109811","url":null,"abstract":"<p><strong>Background: </strong>Impaired wound healing from diabetes mellitus (DM) causes lower limb amputations, posing clinical, social, and economic issues. Hypoxia and advanced glycation end products cause autophagy and apoptosis dysregulation, which delays wound healing. The study will test systemic and topical Nicotinamide Riboside (NR) and Resveratrol (RSV) for the capacity to modulate autophagy and apoptosis via the SIRT-1-FOXO1 pathway and improve diabetic wound healing.</p><p><strong>Methods: </strong>54 male Sprague-Dawley rats were separated into control, diabetic (T1D), T1D-Gel-Base, T1D-NR, T1D-RSV, and T1D-NR+RSV groups. Rats were gavaged with 50 mg/kg/day RSV and 300 mg/kg/day NR for 5 weeks before having their wounds topically treated with 5% NR and RSV gel for 15 days after diabetes induction. Biochemical, histomorphometric, and stereological assays were conducted. The mRNA expressions of SIRT-1, FOXO1, VEGF, BAX, Cas3, Bcl-2, Beclin1, LC3IIβ, P62, and ATG5 were examined by qRT-PCR.</p><p><strong>Results: </strong>NR and RSV improved diabetic rat wound closure. Diabetic rats treated with NR and RSV had significantly higher LC3IIβ, VEGEF, Bcl-2, and SIRT-1 mRNA levels. Bcl-2, p62, and ATG5 were regulated whereas BAX and Cas 3 were reduced. Stereological investigations showed epidermal, dermal, collagen bundle, vascular, and fibroblast density enhancements.</p><p><strong>Conclusion: </strong>This study highlights the potential of NR and RSV, acting as SIRT-1 activators, in improving diabetic wound healing by regulating SIRT-1-FOXO1-mediated autophagy and apoptosis. These findings offer valuable insights for developing targeted strategies to enhance diabetic wound healing. The combination of NR and RSV showed promising effects, suggesting a potential therapeutic approach for improving diabetic wound healing.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109811"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693236","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":"Relationship between blood DNA methylation, diet quality indices and metabolic health: Data from Obekit study.","authors":"Aline Rosignoli da Conceição, Josefina Bressan, Marta Cuervo, Maria Luisa Mansego, J Alfredo Martínez, José Ignacio Riezu-Boj, Fermín I Milagro","doi":"10.1016/j.jnutbio.2024.109805","DOIUrl":"10.1016/j.jnutbio.2024.109805","url":null,"abstract":"<p><p>Epigenetic mechanisms, which can be modulated by dietary factors, have been proposed as a possible factor in understanding interindividual differences in disease susceptibility. We aimed to determine the relationships between DNA methylation (DNAm), diet quality, and metabolic health in Spanish individuals. This is a transversal study encompassing 337 male and female participants in the Obekit study. Diet quality was assessed using a validated semiquantitative food frequency questionnaire and seven previously established scores: overall, healthy and unhealthy Plant-Based Diet Index (PDI, hPDI and uPDI, respectively), dietary diversity score (DDS), unprocessed/minimally processed foods (MPF) and ultra-processed foods (UPF) consumption and Mediterranean diet (MD) score. DNAm was analyzed in white blood cells using the Infinium MethylationEPIC v1.0 BeadChip kit. After filtering by a variance >0.36, we have worked with 5,261 CpG sites. We found four false discovery rate (FDR)-significant correlations between nutrients and CpGs sites: cg00167275 (GLUD1) correlated with alcohol, cg05218090 with folic acid, cg16682935 (PAPSS2) with selenium, and cg09821790 (SLC7A6) with fish food. One differentially methylated region (DMR) located at zinc finger protein gene 57 (ZFP57) was closely related to obesity and specific nutrients, food groups, and diet quality indices. The regression models of diet quality based on DNAm demonstrated that the most predictive values were when UPF and hPDI were considered. Also, UPF and hPDI were the best indices for predicting the main cardiometabolic risk factors. Our finding suggests that specific nutrients and diet quality indices may influence the degree of DNAm and putatively, the metabolic health in Spanish individuals.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109805"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687245","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":"Natural molecule isoliquiritigenin mitigates MASH and liver fibrosis in mice by promoting autophagy through the PI3K/Akt signaling pathway.","authors":"Rong Liu, Yi Zhang, Min Liu, Zhiyin Shang, Shu Song, Yajun Zhang, Yingqun Zhou, Chuantao Tu","doi":"10.1016/j.jnutbio.2024.109808","DOIUrl":"10.1016/j.jnutbio.2024.109808","url":null,"abstract":"<p><p>Isoliquiritigenin (ISL), a flavonoid derived from licorice root, has diverse biological and pharmacological properties. This study aimed to investigate the hepatoprotective effects and mechanism of action of ISL on the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). C57BL/6 mice fed a chow diet or choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) received ISL (10 mg/kg) or vehicle daily via oral administration. To further explore the mechanism of ISL in MASH pathogenesis, AML12 cells were exposed to palmitic acid (PA) as an in vitro model of lipid toxicity. The results showed that, compared with vehicle-treated mice, ISL treatment alleviated liver injury, steatosis, inflammation, and fibrosis in MASH mice. Moreover, ISL treatment reduced the recruitment of CD68⁺ macrophages and activated hepatic stellate cells (HSCs) in MASH livers. In vitro experiments showed that ISL reduced lipid accumulation and mitigated inflammatory responses in PA-induced AML12 cells. Notably, RNA-sequencing analyses revealed that the anti-MASH effect of ISL enhanced autophagy via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. This was further validated by assessing autophagy markers in both MASH liver tissues and PA-stimulated AML12 cells in vitro. Additionally, molecular docking analysis demonstrated that the target proteins of ISL exhibited strong binding affinity to PIK3 isoforms. In conclusion, our findings highlight that ISL mitigates MASH and fibrosis in mice by promoting autophagy through the PI3K/Akt/mTOR signaling pathway, providing reliable evidence to support further studies on MASH in humans.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109808"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687188","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":"Curcumol ameliorates alcohol and high-fat diet-induced fatty liver disease via modulation of the Ceruloplasmin/iron overload/mtDNA signaling pathway.","authors":"Tingting Ding, Wanqing Shen, Wenhui Tao, Junlu Peng, Meijun Pan, Xiaoyu Qi, Wanyu Feng, Na Wei, Shuguo Zheng, Huanhuan Jin","doi":"10.1016/j.jnutbio.2024.109807","DOIUrl":"10.1016/j.jnutbio.2024.109807","url":null,"abstract":"<p><p>Fatty liver disease (FLD), a chronic liver disease characterized by excessive lipid deposition, is affecting more and more people worldwide owing to the increasing global incidence of obesity and heavy alcohol consumption. However, there is still no effective strategy for prevention or treatment of alcohol and high-fat diet (HFD)-induced FLD. The purpose of this study was to investigate the effect of curcumol on alcohol and HFD-induced FLD and the underlying molecular mechanisms. The results showed that curcumol ameliorated alcohol and HFD-induced hepatocyte injury in vivo and in vitro, and the mechanism might be related to its up-regulation of ceruloplasmin and subsequent alleviation of iron overload. Moreover, curcumol inhibited alcohol and HFD-induced mitochondrial damage and mtDNA release in hepatocytes by modulating iron overload. Furthermore, curcumol's inhibition of mtDNA release could suppress the activation of cGAS-STING and subsequent inflammation, and this phenomenon could be reversed by cGAS overexpression. Notably, alcohol and HFD-induced mtDNA release from hepatocytes contributed to HSC activation and this effect could be weakened by curcumol. In conclusion, these findings elucidated that curcumol ameliorated alcohol and HFD-induced FLD via modulating ceruloplasmin/iron overload/mtDNA signaling pathway, which lead to the inhibition of inflammation and HSCs activation.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109807"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644480","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":"Sulforaphane suppresses Aβ accumulation and tau hyperphosphorylation in vascular cognitive impairment(VCI).","authors":"Cong Li, Lei Zhang, Xin Li, Quan Hu, Leilei Mao, Yanxin Shao, Mei Han, Shihao Zhang, Irum Ejaz, Lina Mesbah, Qin Tang, Feifei Shang","doi":"10.1016/j.jnutbio.2024.109803","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109803","url":null,"abstract":"<p><p>Sulforaphane (Sfn) is a compound naturally found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, and kale. It is well-known for its antioxidative and anti-inflammatory effects. Sfn has attracted attention for its potential health benefits, particularly its role in brain health and the potential prevention of dementia and neurodegeneration. Alzheimer's disease (AD) and vascular cognitive impairment (VCI) are the top two causes of dementia. Cerebral vascular lesions give rise to VCI and predispose neurons to degeneration and Alzheimer's disease (AD) by Aβ accumulation and tau hyperphosphorylation. In a rat model of VCI by permanent bilateral common carotid artery occlusion (2VO), we tested the protective effect of the phase II enzyme inducer sulforaphane (Sfn). Sfn ameliorates vascular cognitive deficits by reducing the typical white matter injury and neural atrophy pathological changes in VCI. Moreover, for the first time, we demonstrated that it effectively reduced Aβ and toxic p-tau accumulation in VCI. The protective mechanisms of Sfn involve the induction of HO-1 expression, activation of the Akt/GSK3β pathway, and modulation of amyloid precursor protein (APP) expression levels. Our data suggest that Sfn is a promising therapeutic compound to treat VCI and AD. It inhibits short-term neuron and white matter injuries as well as long-term Aβ and p-tau accumulation caused by cerebral vascular lesions.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109803"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647453","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":"Short term high-fat diet induced liver ILC1 differentiation associated with the TLR9 activation.","authors":"Peng-Fei Hou, Yu Yao, Qian Bai, He-Dong Lang, Yu Qin, Jun-Dong Zhu, Qian-Yong Zhang, Long Yi, Man-Tian Mi","doi":"10.1016/j.jnutbio.2024.109810","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109810","url":null,"abstract":"<p><p>The health impact of dietary fat is a significant nutritional concern. However, the effects of high-fat diet on immune system particularly the liver regional immune function remains still unclear. Liver ILC1 has been recently identified as playing crucial roles in anti-viral defense, liver regeneration, and protection against acute liver injury. Here, in a mouse model, we uncovered that short term high-fat diet for 2 weeks obviously increased the frequency and number of ILC1 in liver. The production of TNF-α and expressions of TRAIL, CXCR3 and CXCR6 were also increased. Furthermore, EASY-RNAseq and ATAC-seq of liver ILC1 clarified the transcriptome characteristics and chromatin accessibility in response to short term high-fat diet, which were involved with lymphocyte differentiation. Mechanistically, we demonstrated that accumulation of liver ILC1 induced by short term high-fat diet was dependent on a TLR9-mediated differentiation through TLR9 inhibitor. Taken together, these findings shed light on the effect and underlying mechanism of short term high-fat diet on liver ILC1 differentiation and provide nutritional strategies and theoretical basis for the liver regional immune function regulation.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109810"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647451","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":"Effects of adding niacinamide to diets with normal and low protein levels on the immunity, antioxidant, and intestinal microbiota in growing-finishing pigs.","authors":"Tianyi Lan, Meiya Cai, Sishen Wang, Yingying Lu, Zhiru Tang, Qingsong Tang, Jingchun Gao, Yetong Xu, Xie Peng, Zhihong Sun","doi":"10.1016/j.jnutbio.2024.109809","DOIUrl":"10.1016/j.jnutbio.2024.109809","url":null,"abstract":"<p><p>This study aimed to investigate the effects of nicotinamide (NAM) applied to diets with different crude protein levels on immune function, antioxidant capacity, and intestinal flora in growing-finishing pigs. Forty barrows (37.0±1.0 kg) were randomly allocated to one of four dietary treatments (n=10 per group). The diets in the two phases consisted of a basal diet with 30 mg/kg NAM, a basal diet with 360 mg/kg NAM, a low-protein diet with 30 mg/kg NAM, and a low-protein diet with 360 mg/kg NAM. The results showed that dietary addition of 360 mg/kg NAM decreased IL-12, malondialdehyde, IgG and IgM contents in the plasma and increased total superoxide dismutase activity and total antioxidant capacity in the colonic mucosa (P < .05). Supplementing the diet with 360 mg/kg NAM increased mRNA expression of the nucleotide-binding oligomerization domain containing 2 and nuclear factor erythroid 2-related factor 2 and protein expression of nuclear factor kappa-B and toll-like receptor 4 in the colonic mucosa (P < .05). The concentrations of acetic acid and butyric acid in the colonic contents and the abundance of Actinobacteriota in the colon at the phylum level were significantly decreased by feeding low-protein diets (P < .05). Additionally, the addition of 360 mg/kg NAM to diets increased (P < .05) the Sobs, Ace, and Chao indices of colonic microorganisms in pigs. Overall, the rational use of NAM can improve inflammatory status, enhance antioxidant capacity and intestinal barrier function, and increase colonic microbial diversity in growing-finishing pigs.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109809"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643491","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":"Neohesperidin protects against colitis-associated colorectal cancer in mice via suppression of the NF-κB/p65 and MAPK pathways.","authors":"Xingyue Cao, Lingling Li, Jianing Hu, Shuhui Zhu, Shuang Song, Siwei Kong, Li Zhou, Yefei Huang","doi":"10.1016/j.jnutbio.2024.109804","DOIUrl":"10.1016/j.jnutbio.2024.109804","url":null,"abstract":"<p><p>Patients with inflammatory bowel disease (IBD) are at increased risk of developing colitis-associated colorectal cancer (CAC). Neohesperidin (NHP), a flavanone glycoside derived from citrus fruits, has been reported to have anti-inflammatory, antioxidant, and anticancer potential. However, the function of NHP on tumorigenesis has not been well understood. To investigate the potential chemopreventive effects of NHP on CAC development, an in vivo azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was used and NHP was administered by daily gavage for 10 weeks throughout the model period. In this study, we found that NHP effectively ameliorated AOM/DSS-induced pathological symptoms of colitis and thus inhibited colon tumorigenesis in mice. NHP treatment attenuated tumor proliferation, induced apoptosis, and inhibited angiogenesis during CAC development. In addition, NHP inhibited macrophage infiltration and reduced the expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and COX-2 at both mRNA and protein levels, and the higher the concentration of NHP, the better the inhibition. It is worth noting that the positive therapeutic agent mesalazine (100 mg/kg) had a therapeutic effect comparable to that of a low concentration of NHP (50 mg/kg), but less effective than the same concentration of NHP (100 mg/kg). In addition, NHP may exert anti-inflammatory and anticancer effects by inhibiting the NF-κB/p65 and ERK/p38 MAPK pathways. Our findings highlight the potential of NHP as a potential therapeutic candidate for IBD and CAC.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109804"},"PeriodicalIF":4.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639201","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 obesity changes the small intestine endocannabinoid system and fecal metabolites of weanling rats associated with reduced intestinal permeability and impaired glucose homeostasis.","authors":"Mariana M Almeida, Camila Calviño, Clara F Reis-Gomes, Isabelle Lombardi, Ana Laura Macedo Brand, Carmen C Pazos-Moura, Rafael Garrett, Marina A Alves, Isis H Trevenzoli","doi":"10.1016/j.jnutbio.2024.109802","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109802","url":null,"abstract":"<p><strong>Purpose: </strong>The small intestine, including the endocannabinoid system (ECS), regulates the energy homeostasis. If maternal obesity modifies the intestinal ECS of the offspring favoring metabolic disorders throughout life is unexplored. Regardless maternal insults, overaction of the ECS has been related to obesity, mainly via type 1 cannabinoid receptor (CB1) signaling, while type 2 cannabinoid receptor (CB2) signaling and the endocannabinoid-like compounds, such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), have been associated with anti-inflammatory effects. We hypothesized that maternal obesity changes the ECS in the small intestine of weanling rat offspring in a sex-specific manner associated with altered fecal metabolites.</p><p><strong>Methods: </strong>Female rats received a control diet (C; 9% fat) or an obesogenic diet (OD; 37.2% fat, 11.8% sucrose) 9 weeks before mating, gestation and lactation. Offspring were euthanized at weaning.</p><p><strong>Results: </strong>Maternal obesity increased CB2 protein content and mRNA levels of monocyte chemoattractant protein-1 in the small intestine in male offspring, while decreased fecal content of PEA and OEA in both sexes. Maternal obesity decreased gut permeability, but impaired glycemic homeostasis. Concerning fecal levels of γ-aminobutyric acid, amino acids and hypoxanthine, maternal obesity induced a fecal signature related to inflammatory and glycemic homeostasis impairment and dysbiosis.</p><p><strong>Conclusions: </strong>Maternal obesity induced intestinal inflammation and the signaling of CB2, PEA, and OEA might be part of a counter-regulatory response, contributing to reduced gut permeability, but not enough to avoid overweight and glycemic impairment in the offspring at weaning. Our findings provide molecular insights into the intestinal and fecal biomarkers for metabolic disorders.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109802"},"PeriodicalIF":4.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639196","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":"Prenatal choline supplementation enhances metabolic outcomes with differential impact on DNA methylation in Wistar rat offspring and dams.","authors":"Jianzhang Dong, Gia V Shelp, Elizabeth M Poole, William J J Cook, Jana Michaud, Clara E Cho","doi":"10.1016/j.jnutbio.2024.109806","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109806","url":null,"abstract":"<p><p>Choline is an essential nutrient required for proper functioning of organs and serves as a methyl donor. In liver where choline metabolism primarily occurs, glucose homeostasis is regulated through insulin receptor substrates (IRS) 1 and 2. Here, we determined the role of prenatal choline as a modulator of metabolic health and DNA methylation in liver of offspring and dams. Pregnant Wistar rat dams were fed an AIN-93G diet and received drinking water either with supplemented 0.25% choline (w/w) as choline bitartrate or untreated control. All offspring were weaned to a high-fat diet for 12 weeks. Prenatal choline supplementation led to higher insulin sensitivity in female offspring at weaning as well as lower body weight and food intake and higher insulin sensitivity in female and male adult offspring compared to offspring from untreated dams. Higher hepatic betaine concentrations were observed in dams and female offspring of choline-supplemented dams at weaning and higher glycerophosphocholine in female and male offspring at post-weaning compared to the untreated control, suggestive of sustaining different choline pathways. Hepatic gene expression of Irs2 was higher in dams at weaning and female offspring at weaning and post-weaning, whereas Irs1 was lower in male offspring at post-weaning. Gene-specific DNA methylation of Irs2 was lower in female offspring at post-weaning and Irs1 methylation was higher in male offspring at post-weaning that exhibited an inverse relationship between methylation and gene expression. In conclusion, prenatal choline supplementation contributes to improved parameters of insulin signaling but these effects varied across time and offspring sex.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109806"},"PeriodicalIF":4.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639206","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}