Lipid Accumulation in HepG2 Cells Is Attenuated by Strawberry Extract through AMPK Activation.

Tamara Forbes-Hernández,Luca Mazzoni,Maurizio Battino,Francesca Giampieri,Bruno Mezzetti,Sadia Afrin,José Quiles,Mario Cordero,Massimiliano Gasparrini

doi:10.3390/nu9060621

Abstract

Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2). For such purpose, the lipid profile and the expression of proteins metabolically related to AMPK were determined on cells lysates. The results demonstrated that strawberry methanolic extract decreased total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides levels (up to 0.50-, 0.30-, and 0.40-fold, respectively) while it stimulated the p-AMPK/AMPK expression (up to 3.06-fold), compared to the control. AMPK stimulation led to the phosphorylation and consequent inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively. Strawberry treatment also entailed a 4.34-, 2.37-, and 2.47-fold overexpression of LDL receptor, sirtuin 1 (Sirt1), and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), respectively, compared to control. The observed results were counteracted by treatment with compound C, an AMPK pharmacological inhibitor, confirming that multiple effects of strawberries on lipid metabolism are mediated by the activation of this protein.

Highlights

Dyslipidemia—a major disorder of lipoprotein metabolism—is one of the main risk factors for cardiovascular diseases (CVDs) including coronary heart disease, heart attacks, strokes, and peripheral vascular disease [1,2,3], which are responsible for most deaths worldwide [4,5]
The phytochemical composition of the strawberry extract demonstrated that the Romina strawberry cultivar is a significant source of polyphenols (2.64 ± 2.63 mg gallic acid equivalent (GAeq)/g fresh weight (FW)), in particular of flavonoids (1.02 ± 0.87 mg catechin equivalent (CATeq)/g
Total Antioxidant Capacity (TAC) of Romina fruits was determined by three a good nutritional quality confirmed a high antioxidant capacity.strawberry variety presents a different methods

Summary

Introduction

Dyslipidemia—a major disorder of lipoprotein metabolism—is one of the main risk factors for cardiovascular diseases (CVDs) including coronary heart disease, heart attacks, strokes, and peripheral vascular disease [1,2,3], which are responsible for most deaths worldwide [4,5]. Low-density lipoprotein (LDL)-cholesterol, and triglycerides levels are correlated with type 2 diabetes, insulin resistance [1], and chronic renal disease [6]. Understanding lipid metabolism is essential for the treatment and prevention of all these pathologies. The AMP-activated protein kinase (AMPK) has been proposed as a potential therapeutic target for the treatment of several chronic diseases including obesity, type 2 diabetes, and CVDs [7,8]. AMPK is a serine/threonine protein kinase that plays a central role in regulating cellular metabolism and energy balance in mammalian cells [9]. When cellular energy stores are depleted by stimuli such as muscle contraction, hypoxia, or myocardial ischaemia, AMPK is activated. AMPK induces ATP generation pathways such as glycolysis, fatty acid oxidation, and lipolysis. Anabolic pathways like gluconeogenesis, and cholesterol and protein synthesis are inhibited

Objectives

Methods

Results

Conclusion