Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1066571 | ENA |
REPOSITORIES: ENA
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Project description:Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the mechanisms underlying are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3’UTR of Dgat2 mRNA and the introns 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3’UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.
2024-04-03 | GSE262777 | GEO
Project description:Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the mechanisms underlying are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3’UTR of Dgat2 mRNA and the introns 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3’UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.
2024-01-10 | GSE252591 | GEO
Project description:In this study, we investigated the effects of organic vegetable juice supplementation on modulating the microbial community, and how its consumption ameliorates blood lipid profiles in diet-induced obese mice. Here, we analyzed the effect of organic vegetable juice on the microbial community and fatty acid synthesis via animal experiments using diet-induced obese mice and continuous colon simulation system. Organic vegetable juice supplement influenced intestinal bacterial composition from phylum to genus level, including decreased Proteobacteria in the ascending colon in the phylum. At the family level, Akkermansia which are associated with obesity, were significantly augmented in the transverse colon and descending colon compared to the control juice group. In addition, treatment with organic vegetable juice affected predicted lipid metabolism function genes related to lipid synthesis. Organic vegetable juice consumption did not have a significant effect on weight loss but helped reduce epididymis fat tissue and adipocytes. Additionally, blood lipid profiles, such as triglyceride, high-density lipoprotein, and glucose, were improved in the organic vegetable juice-fed group. Expression levels of genes related to lipid synthesis, including SREBP-1, PPARγ, C/EBPα, and Fas, were significantly decreased. Analysis of antioxidant markers, including 8-OHdG and MDA, in the vegetable juice group, indicated that blood lipid profiles were improved by the antioxidant effect. These results suggest that organic vegetable juice supplementation may modulate gut microbial community and reduce the potential role of hyperlipidemia in diet-obese mice.
2021-12-31 | GSE171609 | GEO
Project description:The intestinal microbiota is a key regulator of mammalian lipid absorption, metabolism, and storage. Here we show that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long non-coding RNA (lncRNA) Snhg9 in small intestinal epithelial cells. Snhg9 suppressed the activity of the transcription factor peroxisome proliferator–activated receptor γ (PPARγ) – a central regulator of lipid metabolism – by dissociating the PPARγ inhibitor Sirtuin 1 from cell cycle and apoptosis protein 2 (CCAR2). Forced expression of Snhg9 in the intestinal epithelium of conventional mice lowered dietary lipid absorption, reduced body fat, and protected against diet-induced obesity. The microbiota repressed Snhg9 expression through an immune cell signaling relay encompassing myeloid cells and innate lymphoid cells. Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.
2022-07-15 | GSE208020 | GEO
Project description:Intake and absorption of cholesterol (the latter determined by double labeled cholesterol methodology) were nearly unchanged in mice fed the saturated fat diet, but the fecal excretion of neutral sterols (i.e. cholesterol and its microbial conversion products) was increased compared with control diet(+80%; p<0.01). The saturated fat diet did neither significantly affect biliary cholesterol secretion nor intestinal cholesterol absorption (49% vs. 65% in controls, double labeled water methodology, p>0.1). Thus, the increased fecal neutral sterol excretion was primarily due to increased net transintestinal cholesterol excretion (+89% versus control; p<0.05). Since a major fraction of TICE cholesterol absorption is normally reabsorbed (J Lipid Res 2019 Sep;60(9):1562-1572), the increased fecal cholesterol excretion could be due to more transintestinal excretion of cholesterol into the intestinal lumen and/or to its decreased reabsorption. The saturated fat diet increased jejunal expression of genes involved in cholesterol synthesis (Srebf2 and target genes), but did not affect whole body de novo cholesterol synthesis. Conclusion This proof-of-principle study shows that increasing the saturation of the dietary fat can stimulate fecal cholesterol excretion. Individual components of saturated fat diets are to be explored to address the responsible molecular mechanisms
2021-02-01 | GSE37097 | GEO
Project description:Purpose: Obesity and dyslipidemia are associated with increased risk of renal disease.Testosterone deficiency aggravated high-fat diet-induced obesity and hypercholeterolemia. However,whether testosterone deficiency or testosterone deficiency-induced dyslipidemia aggravate the progression of renal disease is not clear. To gain insight into the role of testosterone in modulating renal lipid metabolism, we profiled renal gene expression by RNA-Seq in HFC-fed intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT). Methods: Sexually mature male miniature pigs were either surgical castrated or sham-operated, and castrated with testosterone replacement. We administrated to pigs a high-fat and high-cholesterol (HFC) diet for twelve weeks. RNA-Seq was employed to profile renal gene expression in pigs with different testosterone levels. Conclusions: This study demonstrated that testosterone deficiency aggravated renal lipid accumulation in pigs fed an HFC diet and that these effects could be reversed by testosterone replacement therapy. Impaired metabolic processes, bile acid secretion,estrogen signaling pathway and enhanced triglyceride synthesis may contribute to the increased renal lipid accumulation induced by testosterone deficiency and an HFC diet.
2023-01-17 | GSE125343 | GEO
Project description:In obesity, misalignment of feeding time with the light/dark environment results in disruption of peripheral circadian clocks. Conversely, restricting feeding to the active period mitigates metabolic syndrome through mechanisms that remain unknown. Here we show that adipocyte thermogenesis is essential for the healthful metabolic response to time restricted feeding. Genetic enhancement of adipocyte thermogenesis through ablation of Zfp423 attenuates obesity caused by circadian mistimed high fat diet feeding through a mechanism involving creatine metabolism. Circadian control of adipocyte creatine metabolism underlies timing of diet-induced thermogenesis, and enhancement of adipocyte circadian rhythms through overexpression of the clock activator Bmal1 ameliorates metabolic complications during diet induced obesity. These findings establish creatine mediated diet-induced thermogenesis as a bioenergetic mechanism driving metabolic benefits during time-restricted feeding.
2022-10-24 | GSE181443 | GEO
Project description:Objectives: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. Methods: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcu fl/+ AKO) and Mcu knockout of mice (Mcu fl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. Results: we found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcu fl/+ AKO mice and Mcu fl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcu fl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. Conclusion: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.
2023-11-12 | GSE247235 | GEO
Project description:Bile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis. Male aged matched (~ 12-14 weeks) CYP7A1 transgenic mice and their wild type control littermates were fed a standard chow diet or a high fat (42%) high cholesterol (0.2%) diet (Harlan Teklad #88137) for 4 month Four groups (4 mice/group) are included in the experiments: Group 1: WT _ Chow Group 2: CYP7A1-tg + chow Group 3: WT + Western diet Group 4: CYP7A1-tg _ Western diet Total liver mRNA was isolated with a RNeasy kit (Qiagen) and used for microarray analysis.
2013-08-15 | E-GEOD-38872 | biostudies-arrayexpress
Project description:Purpose: While various functions of peripheral serotonin are known, the direct role of serotonin in regulating hepatic lipid metabolism in vivo is not well understood. We studied whether serotonin directly acts on liver to regulate lipid metabolism. Methods: Methods: 12 weeks aged liver-specific Htr2a KO (Albumin-Cre+/-; Htr2aflox/flox, herein named Htr2a LKO) mice and wildtype (WT) littermates were fed a high-fat diet (HFD, 60% fat calories) for 8 weeks. Results: Hepatic lipid droplet accumulation, NAFLD activity score, and hepatic triglyceride levels were dramatically reduced in HFD-fed Htr2a LKO mice compared to WT littermates. Conclusions: Gut-derived serotonin is a direct regulator of hepatic lipid metabolism via a gut TPH1-liver HTR2A endocrine axis. And shows promise as a novel drug target to ameliorate NAFLD with minimal systemic metabolic effects.
2018-11-27 | GSE120662 | GEO