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N-Acetyl Cysteine Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Intracellular Triglyceride Accumulation by Preserving Mitochondrial Function.

ABSTRACT: Rationale: Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic disease characterized by liver steatosis. Excessive reactive oxygen species (ROS) originating from dysfunctional mitochondria is the major pathophysiological contributor in the development of NAFLD and is thought to be a promising therapeutic target. A few reports demonstrate the antioxidative treatments for NAFLD. Methods: Male C57 mice were fed on a normal chow diet (ND) or high-fat diet (HFD) for 8 weeks. PBS or N-acetyl cysteine (NAC) was gavaged to mice. LO2 human liver cell line treated with palmitic acid (PA) was applied as a cellular model. Western blot, immunofluorescence, biochemistry assay, and pathological staining were used to investigate the mechanism of suppressing lipid accumulation of NAC. Results: NAC treatment was able to prevent HFD-induced NAFLD, as evidenced by less hepatic triglyceride accumulation and lipid droplet formation compared with that of mice in the HFD group. NAC could preserve mitochondrial function by inhibiting excessive mitophagy and promoting mitochondria biogenesis to prevent ROS production. NAC also activated Sirt1 and preserved its protein level and subsequently promoted mitochondria biogenesis via deacetylating PGC1a. Conclusion: We demonstrated that NAC may be an effective drug to treat NAFLD, which was related to its antioxidative and mitochondrial protective effect.

SUBMITTER: Hang W

PROVIDER: S-EPMC8473737 | biostudies-literature |

REPOSITORIES: biostudies-literature

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CSAD Ameliorates Lipid Accumulation in High-Fat Diet-Fed Mice.

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Delphinidin Ameliorates Hepatic Triglyceride Accumulation in Human HepG2 Cells, but Not in Diet-Induced Obese Mice.

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Project description:Non-alcoholic fatty liver disease (NAFLD) affects obesity-associated metabolic syndrome, which exhibits hepatic steatosis, insulin insensitivity and glucose intolerance. Emerging evidence suggests that microRNAs (miRNAs) are essential for the metabolic homeostasis of liver tissues. Many hepatic miRNAs located in the miR-379/miR-544 cluster were significantly increased in leptin-receptor-deficient type 2 mice (db/db), a mouse model of diabetes. However, the function of the miR-379/miR-544 cluster in the process of hepatic steatosis remains unclear. Here, we report that the novel function of miR-379/miR-544 cluster in regulating obesity-mediated metabolic dysfunction. Genetical mutation of miR-379/miR-544 cluster in mice displayed resistance to high-fat diet (HFD)-induced obesity with moderate hepatic steatosis and hypertriglyceridemia. In vitro studies revealed that silencing of miR-379 in human hepatocellular carcinoma (HepG2) cells ameliorated palmitic acid-induced elevation of cellular triglycerides, and overexpression of miR-379 had the opposite effect. Moreover, Igf1r (Insulin-like growth factor 1 receptor) and Dlk1 (Delta-like homolog 1) were directly targeted by miR-379 and miR-329, respectively, and elevated in the livers of the miR-379/miR-544 cluster knockout mice fed on HFD. Further transcriptome analyses revealed that the hepatic gene expressions are dysregulated in miR-379/miR-544 knockout mice fed with HFD. Collectively, our findings identify the miR-379/miR-544 cluster as integral components of a regulatory circuit that functions under conditions of metabolic stress to control hepatic steatosis. Thus, this miRNA cluster provides potential targets for pharmacologic intervention in obesity and NAFLD.

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Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and the leading cause of liver-related deaths worldwide. It has been established that microorganisms are involved in the interaction between the intestinal lumen and the liver; therefore, studies on probiotics as potential candidates are increasing. This study evaluated the effects of Limosilactobacillus fermentum MG4294 and Lactiplantibacillus plantarum MG5289 on NAFLD. The MG4294 and MG5289 reduced lipid accumulation in FFA-induced HepG2 by suppressing the adipogenic proteins through the regulation of AMP-activated protein kinase (AMPK). The administration of these strains in the HFD-induced mice model lowered body weight, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cholesterol levels. In particular, MG4294 and MG5289 restored liver TG and TC to normal levels by lowering lipid and cholesterol-related proteins via the modulation of AMPK in the liver tissue. In addition, the administration of MG4294 and MG5289 reduced pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β-, and IL6) in the intestinal tissues of the HFD-induced mouse model. In conclusion, MG4294 and MG5289 can be presented as probiotics with the potential to prevent NAFLD.

| S-EPMC10143775 | biostudies-literature

Sulforaphane Ameliorates Nonalcoholic Fatty Liver Disease Induced by High-Fat and High-Fructose Diet via LPS/TLR4 in the Gut-Liver Axis.

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