Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

Sep 21, 2018Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

Fisetin may protect the liver from fat buildup by affecting energy regulation and fat breakdown in obese mice on a high-fat diet

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Abstract

Fisetin treatment for 10 weeks led to decreased body weight and liver fat in NAFLD mice.

Mice with nonalcoholic fatty liver disease (NAFLD) showed reduced epididymal adipose tissue weight after fisetin treatment.
Fisetin reduced liver lipid droplets and hepatocyte steatosis in NAFLD mice.
Treatment with fisetin lowered serum concentrations of free fatty acids and leptin.
Fisetin significantly decreased fatty acid synthase levels and increased phosphorylation of AMPKα in liver tissue.
In vitro, fisetin decreased lipid accumulation and enhanced fat breakdown in liver cells.

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BACKGROUND/AIMS: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro.

METHODS: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin.

RESULTS: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes.

CONCLUSION: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

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Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

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