Tomatidine ameliorates obesity-induced nonalcoholic fatty liver disease in mice

Tomatidine is isolated from the leaves and green fruits of some plants in the Solanaceae family, and has been reported to have anti-inflammatory and antitumor effects. Previous studies have found that tomatidine decreases hepatic lipid accumulation via regulation of vitamin D receptor and activation of AMP-activated protein kinase (AMPK) phosphorylation. However, whether tomatidine reduces weight gain and improves nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated how tomatidine ameliorates NAFLD in obese mice and evaluated the regulatory mechanism of lipogenesis in hepatocytes. Male C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity and NAFLD, and treated with tomatidine via intraperitoneal injection. In vitro, FL83B hepatocytes were incubated with oleic acid and treated with tomatidine to evaluate lipid metabolism. Our results demonstrate that tomatidine significantly decreases body weight and fat weight compared to HFD-fed mice. In addition, tomatidine decreased hepatic lipid accumulation and improved hepatocyte steatosis in HFD-induced obese mice. We also found that tomatidine significantly regulated serum total cholesterol, fasting blood glucose, low-density lipoprotein, and triglyceride levels, but the serum high-density lipoprotein and adiponectin concentrations were higher than in the HFD-fed obese mice. In vivo and in vitro, tomatidine significantly suppressed the expression of fatty acid synthase and transcription factors involved in lipogenesis, and increased the expression of adipose triglyceride lipase. Tomatidine promoted the sirtuin 1 (sirt1)/AMPK signaling pathway to increase lipolysis and β-oxidation in fatty liver cells. These findings suggest that tomatidine potentially ameliorates obesity and acts against hepatic steatosis by regulating lipogenesis and the sirt1/AMPK pathway.