Trigonelline prevents high cholesterol and high fat diet induced hepatic lipid accumulation and lipo-toxicity in C57BL/6J mice, via restoration of hepatic autophagy

Food Chem Toxicol. 2018 Nov;121:283-296. doi: 10.1016/j.fct.2018.09.011. Epub 2018 Sep 9.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is often linked with impaired hepatic autophagy. Here, we studied the alterations in hepatocellular autophagy by high cholesterol and high-fat diet (HC-HF) diet in C57BL/6J mice, and by palmitic acid (PA), in AML-12 and HepG2 cells. Further, we analysed role of Trigonelline (TG), a plant alkaloid, in preventing NAFLD, by modulating autophagy. For this, C57BL/6J mice were fed with Standard Chow (SC) or HC-HF diet, with and without TG for 16 weeks. In-vitro; AML-12 cells and HepG2 cells, were exposed to PA with and without TG, for 24 h. Cellular events related to autophagy, lipogenesis, and lipo-toxicity were studied. The HC-HF diet fed mice showed hepatic autophagy blockade, increased triglycerides and steatosis. PA exposure to AML-12 cells and HepG2 cells induced impaired autophagy, ER stress, resulting in lipotoxicity. TG treatment in HC-HF fed mice, restored hepatic autophagy, and prevented steatosis. TG treated AML-12, and HepG2 cells exposed to PA showed autophagy restoration, and reduced lipotoxicity, however, these effects were diminished in Atg7-/- HepG2 cells, and in the presence of chloroquine. This study shows that HC-HF diet-induced impaired autophagy, and steatosis is prevented by TG, which attributes to its novel mechanism in treating NAFLD.

Keywords: Autophagy; NAFLD; Trigonelline.

MeSH terms

  • Alkaloids / pharmacology*
  • Animal Feed / analysis
  • Animals
  • Autophagy / drug effects*
  • Autophagy-Related Protein 7 / genetics
  • Autophagy-Related Protein 7 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cholesterol / administration & dosage*
  • Diet, High-Fat / adverse effects*
  • Fatty Liver / chemically induced*
  • Fatty Liver / prevention & control
  • Gene Silencing
  • Humans
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Up-Regulation
  • Weight Gain

Substances

  • Alkaloids
  • trigonelline
  • Cholesterol
  • Atg7 protein, human
  • Autophagy-Related Protein 7