Nobiletin Inhibits Hepatic Lipogenesis via Activation of AMP-Activated Protein Kinase.

Taewon Yuk,Heon Sang Jeong,Jeehye Sung,Younghwa Kim,Junsoo Lee,Jinwoo Yang

doi:10.1155/2018/7420265

Abstract

We aimed to investigate the effects of nobiletin on hepatic lipogenesis in high glucose-induced lipid accumulation in HepG2 cells. Nobiletin, a citrus polymethoxyflavonoid with six methoxy groups, is present abundantly in the peels of citrus fruits. HepG2 cells were incubated in Dulbecco's modified Eagle's medium containing high glucose (25 mM) and subsequently treated with nobiletin at different concentrations (5, 25, and 50 μM). Results showed that nobiletin markedly inhibited high glucose-induced hepatic lipid accumulation in HepG2 cells. In addition, it reduced the protein expression of lipogenic factors, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Nobiletin significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Pretreatment with compound C, an AMPK inhibitor, abolished the inhibitory effects of nobiletin on SREBP-1c and FAS expression. These results suggested that nobiletin might attenuate high glucose-induced lipid accumulation in HepG2 hepatocytes via modulation of AMPK signaling pathway. Therefore, nobiletin might be useful for the prevention and treatment of nonalcoholic fatty liver diseases.

Highlights

The liver plays a key role in lipid metabolism
Accumulation of lipid droplets in the hepatocytes has been closely related to obesity, insulin resistance, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD) [2, 3]
Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), trypsin-ethylenediaminetetraacetic acid (EDTA), and penicillin-streptomycin were obtained from Gibco BRL (Grand Island, NY, USA). 6-[4-(2-Piperidin-1-ylethoxy)phenyl]-3pyridin-4-ylpyrazolo[1,5-a]pyrimidine (Compound C), 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), dimethyl sulfoxide (DMSO), lactate dehydrogenase (LDH) kit, and Oil red O (ORO) were purchased from SigmaAldrich

Summary

Introduction

The liver plays a key role in lipid metabolism. Accumulation of lipid droplets in the hepatocytes has been closely related to obesity, insulin resistance, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD) [2, 3]. Hepatic AMP-activated protein kinase (AMPK) is thought to play a pivotal role in regulating lipid metabolism, glucose homeostasis, and insulin sensitivity [7, 8]. Sterol regulatory elementbinding proteins (SREBPs) are key lipogenic transcription factors that regulate the expression of lipogenic enzymes, including ACC, fatty acid synthase (FAS), and 3-hydroxy3-methylglutaryl-CoA reductase [10,11,12]. The phosphorylation of AMPK inactivates SREBP-1 and inhibits hepatic lipid accumulation in a high-fat diet-induced mouse [14, 15]

Objectives

Methods

Conclusion