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
; 121: 283-296, 2018 Nov.
Article
em En
| MEDLINE
| ID: mdl-30208301
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-12â¯cells and HepG2 cells, were exposed to PA with and without TG, for 24â¯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-12â¯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.
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Colesterol
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Alcaloides
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Fígado Gorduroso
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Dieta Hiperlipídica
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article