Combined Metabolic Activators Decrease Liver Steatosis by Activating Mitochondrial Metabolism in Hamsters Fed with a High-Fat Diet
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ABSTRACT:
PROVIDER: PRJNA772762 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16490800_1.fastq.gz | Fastqsanger.gz | |||
| SRR16490800_2.fastq.gz | Fastqsanger.gz | |||
| SRR16490801_1.fastq.gz | Fastqsanger.gz | |||
| SRR16490801_2.fastq.gz | Fastqsanger.gz | |||
| SRR16490802_1.fastq.gz | Fastqsanger.gz |
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Project description:The impairment of the intestinal barrier will lead to the accumulation of fat and harmful substances in the liver, inducing hepatic steatosis or steatohepatitis. Zhang et al. identified NSD2 in the intestine as a novel and essential regulator of hepatic steatosis. NSD2 directly regulates transcriptional activation of ERN1 through the modification of H3 dimethylated on lysine 36 (H3K4me36), thereby activating the ERN1-JNK axis to induce inflammatory response, intestinal barrier impairment, and hepatic steatosis. This functional mechanism of NSD2 provides a potential therapeutic target for this disease.
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Project description:Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide. Hypercholesterolemia is a risk factor of atherosclerosis. This study evaluated the effects of three doses of Totum-070 (3.5%, 4.25% and 5% of diet for 12 weeks; HFD-Totum-070 groups), a plant-based polyphenol-rich supplement, in hamsters with high-fat diet (HFD)-induced dyslipidemia (HFD group). Several functional tests were performed in vivo to characterize the effect of Totum-070 on lipoprotein metabolism. Molecular mechanisms of action were explored using human Caco2 enterocytes. Totum-070 supplementation reduced total cholesterol (-41%), non-HDL cholesterol (-47%) and triglycerides (-46%) in a dose-dependent manner, compared with HFD, without any effects on food intake or body weight. HFD-induced steatosis also was significantly decreased. Gene expression analysis in liver and intestine highlighted Totum-070 effects on metabolic pathways and a strong anti-inflammatory effect. Upon challenge with olive oil gavage, post-prandial lipemia was strongly reduced. Sterol excretion in the feces was increased in the HFD-Totum-070 groups compared with the HFD group. The dual isotope cholesterol absorption test confirmed the reduction of intestinal cholesterol absorption in Totum-070 supplemented hamsters. These effects were confirmed in Caco2 cells where incubation with Totum-070 inhibited cholesterol uptake and apolipoprotein B secretion. Furthermore, metagenomic analysis of gut microbiota revealed a strong effect of Totum-070 on alpha and beta diversity measures. Compared with the HFD group, the Firmicutes to Bacteroidetes ratio was beneficially reduced in the HFD-hamsters supplemented with Totum-070 groups. Altogether, these findings indicate that Totum-070-mediated inhibition of intestinal cholesterol absorption limits the rise in blood cholesterol in high-fat fed hamsters.
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