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.