Journal of Nutritional Biochemistry最新文献

{"title":"Proposed receptor-mediated mechanisms of melatonin in nitroglycerin-induced migraine-like hyperalgesic conditions in rats.","authors":"Erkan Kilinc, Ibrahim Ethem Torun, Yasemin Baranoglu Kilinc, Fatma Töre","doi":"10.1016/j.jnutbio.2024.109800","DOIUrl":"10.1016/j.jnutbio.2024.109800","url":null,"abstract":"<p><p>Melatonin has a therapeutic effect on migraine, but the mechanisms underlying its antimigraine effect have not been elucidated. This study therefore investigated for the first time the receptor-mediated mechanisms of action of melatonin in nitroglycerin (NTG)- induced migraine-like hyperalgesic conditions in rats. Melatonin, nonselective MT1/MT2 antagonist luzindole, selective MT2 antagonist DH97 or potent MT3 antagonist prazosin, alone or in various combinations, were administered to NTG-induced migraine rats and ex-vivo meningeal preparations. Basal and drug-treated pain behaviors were assessed with the von-Frey test. CGRP levels in the trigeminal ganglia, trigeminal nucleus caudalis (TNC) and ex-vivo superfusate medium, as well as c-fos level in the TNC, were measured by ELISA. Meningeal mast cells were stained with toluidine-blue and examined histologically for their activation and count. Melatonin mitigated mechanical hyperalgesia, and c-fos and CGRP expression in the TNC, CGRP expression in trigeminal ganglia, CGRP release from meningeal afferents, all of which were induced by NTG, and also suppressed NTG-stimulated meningeal mast cell activation. The effects of melatonin were abolished in the presence of luzindole and DH97, respectively. However, prazosin did not reverse the effects of melatonin except for mechanical hyperalgesia. Luzindole and DH97 in combinations with prazosin also canceled the effects of melatonin, respectively, other than CGRP expression in the TNC. Melatonin exerts its anti-hyperalgesic effects through modulation of trigeminal expression and meningeal release of CGRP, and meningeal mast cell activation in experimental migraine-like conditions. The effects of melatonin are mainly mediated by MT2 receptors, without excluding a possible role for MT1.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109800"},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622453","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":"Trans 10, cis 12-conjugated linoleic acid in low concentration reduces while in high concentration enhances adipocyte metabolism but effectively improves hepatic steatosis of obese mice.","authors":"Yu Rao, Shui Yu, Luwen Liang, Qi Wang, Jiaqi Lu, Baozhu Wang, Kemian Gou","doi":"10.1016/j.jnutbio.2024.109801","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109801","url":null,"abstract":"<p><p>Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA)-producing mice were used to investigate the anti-obesity of obese males. Compared to wild-type littermates, high concentration t10c12-CLA in biallelic Pai/Pai mice reduced fat by up-regulation lipid metabolism in white adipose tissue (WAT). In contrast, low concentration t10c12-CLA in monoallelic Pai/wt mice could not reduce fat for down-regulation lipid metabolism in WAT. Simultaneously, t10c12-CLA enhanced thermogenesis and beta-oxidation in brown adipose tissue, alleviated steatosis by declining lipid metabolism in the liver, and lowered circulating triglycerides. On the other hand, low concentration t10c12-CLA specifically resulted in decreased circulating fibroblast growth factor 21, elevated glucose and high-density lipoprotein, whereas high concentration t10c12-CLA specifically increased circulating and hepatic cholesterol levels via up-regulation of low-density lipoprotein receptor in the liver. In conclusion, high concentration t10c12-CLA enhances local lipid metabolism in WAT and leads to fat loss, whereas low concentration t10c12-CLA attenuates the enzymic activities in WAT and fails to reduce fat. T10c12-CLA can effectively and concentration independently improve steatosis by attenuating hepatic lipid metabolism. These results suggest that low concentration of t10c12-CLA is beneficial, but high concentration is unfavorable to obese male mammals.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109801"},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622454","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 supplementation spermidine during gestation improves placental angiogenesis and reproductive performance of high prolific sows.","authors":"Bingbing Duan, Sijiao Ran, Lin Wu, Tianci Dai, Jian Peng, Yuanfei Zhou","doi":"10.1016/j.jnutbio.2024.109792","DOIUrl":"10.1016/j.jnutbio.2024.109792","url":null,"abstract":"<p><p>Spermidine (SPD) is a widely recognized polyamine compound found in mammalian cells and plays a key role in various cellular processes. We propose that SPD may enhance placental vascular development in pregnant sows, leading to increased birth weight of piglets. Six hundred and nine sows at 60 days of gestation were randomly assigned into a basal diet (CON group), basal diet supplemented 10 mg/kg of SPD (SPD1 group), and basal diet supplemented 20 mg/kg of SPD (SPD2 group), respectively. Compared with the CON, SPD1 significantly increased the average number of healthy piglets per litter and the placental efficiency (P < .05), while the average number of mummified fetus per litter and the percentage of weak piglets significantly decreased (P < .05). In the plasma metabolomics, SPD content in plasma of sows (P = .075) and umbilical cord plasma of piglets (P = .078) had an increasing trend in response to SPD1. Furthermore, SPD1 increased the expression of the vascular endothelial cell marker protein, platelet endothelial cell adhesionmolecule-1 (PECAM-1/CD31) and the density of placental stromal vessels (P < .05). Moreover, as compared to CON, SPD2 significantly decreased the average number of mummified fetus per litter (P < .05), while the placental efficiency and the expression of amino acid transporter solute carrier (SLC) family 7, member7 (SLC7A7) and glucose transporters SLC2A2) and SLC5A4 in placental tissue significantly increased (P < .05). These results suggest that maternal supplementation of SPD during pregnancy increased healthy litter number, and promoted placental tissue development. Our findings provide evidence that maternal SPD has the potential to improve the production performance of sows.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109792"},"PeriodicalIF":4.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567380","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":"Oral administration of PIISVYWK and FSVVPSPK peptides attenuates obesity, oxidative stress, and inflammation in high fat diet-induced obese mice.","authors":"Indyaswan T Suryaningtyas, Chathuri K Marasinghe, Bonggi Lee, Jae-Young Je","doi":"10.1016/j.jnutbio.2024.109791","DOIUrl":"10.1016/j.jnutbio.2024.109791","url":null,"abstract":"<p><p>The bioactive peptides PIISVYWK (P1) and FSVVPSPK (P2), derived from the blue mussel Mytilus edulis, exhibit significant benefits in combating obesity, oxidative stress, and inflammation. This study demonstrates that these peptides inhibit the differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) into adipocytes by downregulating the adipogenic transcription factors peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1). Furthermore, P1 and P2 reduce lipogenesis and enhance lipolysis through the activation of AMP-activated protein kinase (AMPK) and hormone-sensitive lipase (HSL). These peptides also decrease intracellular reactive oxygen species (ROS) generation during adipogenesis and inhibit the mitogen-activated protein kinase (MAPK) pathway, thereby reducing inflammation. The involvement of heme oxygenase-1 (HO-1) in this mechanism is confirmed by the reversal of these effects upon HO-1 inhibition. In vivo, oral administration of P1 and P2 in high-fat diet (HFD) obese mice prevents weight gain, reduces adipose tissue accumulation, lowers adipogenic and lipogenic biomarkers, improves serum cholesterol levels, enhances lipolysis, and decreases pro-inflammatory cytokine production. These findings suggest that P1 and P2 peptides may effectively prevent obesity and related metabolic disorders by activating the HO-1/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109791"},"PeriodicalIF":4.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567504","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":"Single-cell and spatial transcriptomes reveal the impact of maternal low protein diet on follicular cell composition and ovarian micro-environment in the offspring.","authors":"Zheng-Hui Zhao, Lin-Jian Gu, Xiao-Guohui Zhang, Zhen-Bo Wang, Xiang-Hong Ou, Qing-Yuan Sun","doi":"10.1016/j.jnutbio.2024.109789","DOIUrl":"10.1016/j.jnutbio.2024.109789","url":null,"abstract":"<p><p>Maternal low protein diet around pregnancy reduces the primordial follicles in offspring ovary. Resolving cellular and molecular mechanisms associated with low protein diet is therefore urgently needed for the guidance of dietary interventions. Here, we utilized single-cell and spatial RNA-seq to create transcriptomic atlases of offspring ovaries from maternal low protein diet mice. Analysis of cell type specific low protein diet associated transcriptional changes revealed increased unfolded protein and decreased oxidative phosphorylation defense as a hallmark of low protein diet effects. Altered pathways included hedgehog signaling in granulosa cells, BMP signaling in theca cells and PTN signaling in early theca cells. Notably, the disordered follicular cell function and ovarian microenvironment may closely corelated with decreased follicular number and quality. Collectively, our findings depict the transcriptomic atlases of the offspring ovary derived from maternal low protein diet group and provide candidate molecular mechanisms underlying the complex ovarian cell changes conferred by low protein diet.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109789"},"PeriodicalIF":4.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567684","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":"PBMC transcriptome reveals an early metabolic risk profile in young rats with metabolically obese, normal-weight phenotype.","authors":"Carmen García-Ruano, Andrea Costa, Andreu Palou, Paula Oliver","doi":"10.1016/j.jnutbio.2024.109790","DOIUrl":"10.1016/j.jnutbio.2024.109790","url":null,"abstract":"<p><p>Metabolically obese, normal-weight (MONW) phenotype is characterized by visceral adiposity and obesity-related complications despite the absence of excess body weight. Early identification of this phenotype is crucial to establish preventive strategies. We aim to validate the utility of peripheral blood mononuclear cells (PBMC) transcriptome to detect metabolic risk related to the MONW phenotype at early life stages (young adulthood). Male Wistar rats were pair-fed either standard (NW group) or a high-fat diet (MONW group) after weaning, until 3.5 months. Global gene expression was examined by microarray in PBMC, and specific genes of interest by RT-qPCR in PBMC and liver. Results were validated in adult 6-month-old MONW rats. Young MONW animals had similar weight to controls (NW group) but greater adiposity, including liver fat content, and insulin resistance signs. PBMC transcriptome distinguished clearly MONW from NW rats. Neurological pathways were affected in line with impaired cognition in these animals. Most top-regulated genes were related to inflammation, including the top-up and down-regulated genes, Hpgds and Slfn4. Expression of fatty liver-related genes like Mkrn1 and Nampt was also affected in PBMC of the young MONW group mirroring liver alteration. Slfn4 and Mkrn1 appeared as especially relevant biomarkers with altered expression also in PBMC of adult 6-month-old MONW rats. In conclusion, PBMC transcriptomic analysis emerges as a tool for identifying early biomarkers of obesity-related metabolic risk in young and apparently healthy (lean) subjects, pointing towards increased inflammation, liver fat deposition, and cognitive alterations.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109790"},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567718","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":"Retinol metabolism signaling participates in microbiota-regulated fat deposition in obese mice.","authors":"Hui Han, Shunfen Zhang, Mengyu Wang, Bao Yi, Yong Zhao, Martine Schroyen, Hongfu Zhang","doi":"10.1016/j.jnutbio.2024.109787","DOIUrl":"10.1016/j.jnutbio.2024.109787","url":null,"abstract":"<p><p>Obesity is a global pandemic threatening public health, excess fat accumulation and overweight are its characteristics. In this study, the interplay between gut microbiota and retinol metabolism in modulating fat accumulation was verified. We observed gut microbiota depletion reduced the body weight and the ratios of white adipose tissues (WATs) to body weight in high-fat diet (HFD) fed-mice. The kyoto encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network of RNA-seq results indicated that retinol metabolism signaling may be involved in the microbiota-regulated fat deposition. Furthermore, activated retinol metabolism signaling by all-trans retinoic acid (atRA) supplementation reduced body weight and WAT accumulation in obese mice. 16S rRNA gene sequencing of the ileal microbiota suggested that atRA supplementation increased the microbial diversity and induced the growth of beneficial bacteria including Parabacteroides, Bacteroides, Clostridium_XVIII, Bifidobacterium, Enterococcus, Bacillus, Leuconostoc, and Lactobacillus in obese mice. Spearman correlation showed that the microbiota altered by atRA were associated with body and WAT weights. Together, this study reveals the interaction between the gut microbiota and retinol metabolism signaling in regulating adipose accumulation and obesity. It is expected of this finding to provide new insights to prevent and develop therapeutic measures of obesity-related metabolic syndrome.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109787"},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502431","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":"Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl₄-induced subacute hepatic injury based on LC-MS/MS.","authors":"Yiming Ni, Xinghua Chen, Yiqun Jia, Long Chen, Mingmei Zhou","doi":"10.1016/j.jnutbio.2024.109788","DOIUrl":"10.1016/j.jnutbio.2024.109788","url":null,"abstract":"<p><p>Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl₄ induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl₄, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl₄, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"109788"},"PeriodicalIF":4.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502430","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":"Butyrolactone-I from marine fungi alleviates intestinal barrier damage caused by DSS through regulating lactobacillus johnsonii and its metabolites in the intestine of mice","authors":"Shengwei Chen ,&nbsp;Xueting Niu ,&nbsp;Yi Zhang ,&nbsp;Jiaying Wen ,&nbsp;Minglong Bao ,&nbsp;Yin Li ,&nbsp;Yuan Gao ,&nbsp;Xinchen Wang ,&nbsp;Xiaoxi Liu ,&nbsp;Yanhong Yong ,&nbsp;Zhichao Yu ,&nbsp;Xingbing Ma ,&nbsp;Jong-Bang Eun ,&nbsp;Jae-Han Shim ,&nbsp;A. M. Abd El-Aty ,&nbsp;Xianghong Ju","doi":"10.1016/j.jnutbio.2024.109786","DOIUrl":"10.1016/j.jnutbio.2024.109786","url":null,"abstract":"<div><div>Butyrolactone-I (BTL-1), a secondary metabolite from the marine fungus <em>Aspergillus terreus</em>, exhibits numerous biological activities. Previous research has indicated that Butyrolactone-I alleviates intestinal epithelial inflammation via the TLR4/NF-κB and MAPK pathways. However, the mechanisms underlying its protection against intestinal barrier damage remain unclear. This study aims to further elucidate these mechanisms. We observed that BTL-1 administration increased the abundance of <em>Lactobacillus johnsonii</em> (<em>LJ</em>) in both <em>in vivo</em> and <em>in vitro</em> experiments, prompting an investigation into the effects of <em>LJ</em> and its metabolites on DSS-induced inflammatory bowel disease (IBD). The results demonstrated that BTL-1 significantly upregulated tight junction (TJ) and adherens junction (AJ) proteins, maintained intestinal barrier integrity, and alleviated DSS-induced IBD in mice. These effects were associated with the proliferation of <em>LJ</em> and its metabolites, such as butyric and propionic acids, and the inhibition of the MAPK signaling pathway in the colon. Interestingly, administering <em>LJ</em> alone produced a protective effect against DSS-induced IBD similar to that observed with BTL-1. Furthermore, butyric acid, a metabolite of <em>LJ</em>, also upregulated TJ/AJ proteins in intestinal epithelial cells through the MAPK signaling pathway. Our findings suggest that BTL-1 regulates intestinal flora, promotes LJ proliferation, protects intestinal barrier integrity, increases the concentrations of butyric and propionic acids, and ultimately inhibits the activation of the MAPK signaling pathway in mice to alleviate IBD. Therefore, BTL-1 could potentially be used as a natural drug to prevent IBD and maintain intestinal flora balance. We explored how butyrolactone-I exerts a preventive effect on IBD through intestinal bacteria (<em>Lactobacillus johnsonii</em>).</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109786"},"PeriodicalIF":4.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502417","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":"Impact of reduced hepatic ceramide levels in high-fat diet mice on glucose metabolism","authors":"Monika Imierska ,&nbsp;Piotr Zabielski ,&nbsp;Kamila Roszczyc-Owsiejczuk ,&nbsp;Karolina Pogodzińska ,&nbsp;Agnieszka Błachnio-Zabielska","doi":"10.1016/j.jnutbio.2024.109785","DOIUrl":"10.1016/j.jnutbio.2024.109785","url":null,"abstract":"<div><div>Dysregulation of insulin action in hepatocytes, common in obesity, significantly contributes to insulin resistance, type 2 diabetes, and metabolic syndrome. Previous research highlights ceramides' role in these conditions. This study explores the impact of ceramides by silencing the serine palmitoyltransferase (<em>Sptlc2</em>) gene, crucial for the initial ceramide biosynthesis, using hydrodynamic gene delivery. Male C57BL/6 mice were randomly divided into three groups: one on a low-fat diet (LFD) receiving scrambled shRNA plasmids, another on a high-fat diet (HFD) with scrambled shRNA plasmids, and a third on HFD with a plasmid targeting Sptlc2. Analyses included RT-PCR for gene expression, western blot for protein levels, and UHPLC/MS/MS for lipid profiling. Glucose metabolism was evaluated via oral glucose tolerance tests, homeostatic model assessment of insulin resistance, and glucose-6-phosphate analysis. Results showed that HFD induces insulin resistance by inhibiting insulin signaling and increasing active lipid levels in hepatocytes. <em>Sptlc2</em> silencing reduced ceramide accumulation, improving insulin signaling and glucose metabolism. Notably, ceramide synthesis inhibition did not significantly affect other lipid levels, highlighting ceramide's critical role in hepatic insulin resistance.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109785"},"PeriodicalIF":4.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468093","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}