Lonicera caerulea Extract Attenuates Non-Alcoholic Fatty Liver Disease in Free Fatty Acid-Induced HepG2 Hepatocytes and in High Fat Diet-Fed Mice.

Miey Park,Hae-Jeung Lee,You-Suk Lee,Jeong-Hyun Yoo

doi:10.3390/nu11030494

Abstract

Honeyberry (Lonicera caerulea) has been used for medicinal purposes for thousands of years. Its predominant anthocyanin, cyanidin-3-O-glucoside (C3G), possesses antioxidant and many other potent biological activities. We aimed to investigate the effects of honeyberry extract (HBE) supplementation on HepG2 cellular steatosis induced by free fatty acids (FFA) and in diet-induced obese mice. HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without HBE. Obesity in mice was induced by a 45% high fat diet (HFD) for 6 weeks and subsequent supplementation of 0.5% HBE (LH) and 1% HBE (MH) for 6 weeks. HBE suppressed fatty acid synthesis and ameliorated lipid accumulation in HepG2 cells induced by FFA. Moreover, HBE also decreased lipid accumulation in the liver in the supplemented HBE group (LH, 0.5% or MH, 1%) compared with the control group. The expressions of adipogenic genes involved in hepatic lipid metabolism of sterol regulatory element-binding protein-1 (SREBP-1c), CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid synthase (FAS) were decreased both in the HepG2 cells and in the livers of HBE-supplemented mice. In addition, HBE increased mRNA and protein levels of carnitine palmitoyltransferase (CPT-1) and peroxisome proliferator-activated receptor α (PPARα), which are involved in fatty acid oxidation. Furthermore, HBE treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and Acetyl-CoA Carboxylase (ACC). Honeyberry effectively reduced triglyceride accumulation through down-regulation of hepatic lipid metabolic gene expression and up-regulation of the activation of AMPK and ACC signaling in both the HepG2 cells as well as in livers of diet-induced obese mice. These results suggest that HBE may actively ameliorate non-alcoholic fatty liver disease.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, resulting from excessive accumulation of lipids in the liver despite a low level of alcohol consumption [1,2].Recent increases in the prevalence of obesity and obesity-related metabolic disorders have demonstrated parallelism with a global increase in NAFLD [3,4]
Honeyberry effectively reduced triglyceride accumulation through down-regulation of hepatic lipid metabolic gene expression and up-regulation of the activation of AMPK and Acetyl-CoA Carboxylase (ACC) signaling in both the HepG2 cells as well as in livers of diet-induced obese mice. These results suggest that honeyberry extract (HBE) may actively ameliorate non-alcoholic fatty liver disease
HBE treatment at a concentration of up to 1000 μg/mL with 1 mM free fatty acids (FFA) for 24 h did not demonstrate a significant decrease in cell viability (Figure 2)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, resulting from excessive accumulation of lipids in the liver despite a low level of alcohol consumption [1,2]. Recent increases in the prevalence of obesity and obesity-related metabolic disorders have demonstrated parallelism with a global increase in NAFLD [3,4]. More than 20% of adults in western countries are diagnosed with NAFLD, and its prevalence increases from 70 to 90% among people who are obese or suffer from diabetes [5]. NAFLD is significantly associated with an increased risk of cardiovascular diseases [6]. Excessive accumulation of triglycerides (TG) due to esterification of glycerol and free fatty acid (FFA)

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