Capsaicin Targets Lipogenesis in HepG2 Cells Through AMPK Activation, AKT Inhibition and PPARs Regulation.

Alicia Bort,Inés Díaz-Laviada,Pedro Mateos-Gómez,Belén Sánchez,Nieves Rodríguez-Henche

doi:10.3390/ijms20071660

Alicia Bort, Inés Díaz-Laviada + Show 3 more

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https://doi.org/10.3390/ijms20071660

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Abstract

Obesity, a major risk factor for chronic diseases such as type 2 diabetes (T2D), represents a serious primary health problem worldwide. Dietary habits are of special interest to prevent and counteract the obesity and its associated metabolic disorders, including lipid steatosis. Capsaicin, a pungent compound of chili peppers, has been found to ameliorate diet-induced obesity in rodents and humans. The purpose of this study was to examine the effect of capsaicin on hepatic lipogenesis and to delineate the underlying signaling pathways involved, using HepG2 cells as an experimental model. Cellular neutral lipids, stained with BODIPY493/503, were quantified by flow cytometry, and the protein expression and activity were determined by immunoblotting. Capsaicin reduced basal neutral lipid content in HepG2 cells, as well that induced by troglitazone or by oleic acid. This effect of capsaicin was prevented by dorsomorphin and GW9662, pharmacological inhibitors of AMPK and PPARγ, respectively. In addition, capsaicin activated AMPK and inhibited the AKT/mTOR pathway, major regulators of hepatic lipogenesis. Furthermore, capsaicin blocked autophagy and increased PGC-1α protein. These results suggest that capsaicin behaves as an anti-lipogenic compound in HepG2 cells.

Highlights

Obesity promotes alterations in hepatic lipid and glucose metabolism, which are intimately linked to the development of non-alcoholic fatty liver disease (NAFLD) [1]
Ectopic accumulation of lipids within the liver causes metabolic disturbances that contribute to the development of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) [2,4,5]
Liver PPARγ expression is relatively low in basal conditions, it acts as a steatogenic factor [18] and its expression is upregulated in fatty liver diseases such as NAFLD, where it induces de novo lipogenesis and lipid accumulation [19]

Summary

Introduction

Obesity promotes alterations in hepatic lipid and glucose metabolism, which are intimately linked to the development of non-alcoholic fatty liver disease (NAFLD) [1]. Ectopic accumulation of lipids within the liver causes metabolic disturbances that contribute to the development of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) [2,4,5]. Metformin and thiazolidinediones (TZDs) act as potent insulin sensitizers and are widely used as antidiabetic agents. Both increase peripheral glucose uptake, decrease fasting fatty acid concentration, increase circulating adiponectin concentration and decrease pro-inflammatory cytokines [8,9]. Metformin reverses fatty liver disease in obese, leptin-deficient mice [10] and has beneficial effects in NAFLD patients [11]. Liver PPARγ expression is relatively low in basal conditions, it acts as a steatogenic factor [18] and its expression is upregulated in fatty liver diseases such as NAFLD, where it induces de novo lipogenesis and lipid accumulation [19]

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