Oligonol suppresses lipid accumulation and improves insulin resistance in a palmitate-induced in HepG2 hepatocytes as a cellular steatosis model

Abstract

BackgroundOligonol is a low molecular weight form of polyphenol polymers derived from lychee fruits. Several studies suggest that Oligonol has an anti-obesity effect. Since obesity is tightly associated with insulin resistance, we investigated a possible remission effect of Oligonol on lipid accumulation and insulin resistance in human hepatic HepG2 cells.MethodsHepG2 cells were treated with palmitate for 24 h to induce cellular hepatic steatosis and insulin resistance. The cells were then treated with Oligonol at subtoxic concentrations and examined for lipid metabolism, cytokine production, and insulin signaling using quantitative RT-PCR and western blot analysis.ResultsOligonol treatment reversed the palmitate-induced intracellular lipid accumulation, down regulated the expression of lipogenic genes, and up-regulated genes for fatty acid degradation. Oligonol restored insulin sensitivity, as was determined by the phosphorylation states of IRS-1. Oligonol also inhibited STAT3-SOCS3 signaling and increased AMPK phosphorylation in HepG2 cells.ConclusionOligonol treatment improved palmitate-induced cellular steatosis and insulin resistance in HepG2 cells with concomitant reduction of inflammatory cytokines and decrease in STAT3-SOCS3 and AMPK-mTOR pathways. Oligonol may have beneficial effects in lipid metabolism and insulin resistance in the liver.

Flavanol‐rich lychee fruit extract alleviates diet‐induced insulin resistance via suppressing mTOR/SREBP‐1 mediated lipogenesis in liver and restoring insulin signaling in skeletal muscle

“…In this context, the possible molecular mechanism of oligonol in alleviating hepatic insulin resistance was through suppressed mTOR/S6K1 signaling pathway under the condition of nutrient overload. In line with our in vivo experiments, activation of AMPK, inhibition of mTOR/S6K1, and decreased serine phosphorylation by oligonol has been reported by palmitate induced‐insulin resistance in HepG2 hepatocytes . Selective inhibitors of PTEN and GSK3α have been shown to improve insulin sensitivity in animal models of diabetes and obesity .…”

“…Many recent studies further demonstrated that, similar to EGCG, oligonol inhibited adipogenesis via suppressing Akt/mTOR (mammalian target of rapamycin) and enhanced lipolysis via extracellular‐signal‐regulated kinases (ERK) activation in adipocytes . Furthermore, oligonol suppressed lipid accumulation via enhancing AMP‐activated protein kinase (AMPK) activation and inhibiting mTOR‐S6K (ribosomal protein S6 kinase) pathway in palmitate induced‐insulin resistance in HepG2 hepatocytes . In vitro evidence suggests that oligonol exhibits beneficial effects on obesity‐related metabolic disorders, however, no direct in vivo evidence systemically investigate the relationship between peripheral lipid metabolism and insulin resistance upon treatment with oligonol.…”

Dual‐Specificity Phosphatase 9 Protects Against Nonalcoholic Fatty Liver Disease in Mice Through ASK1 Suppression

“…A,B). To determine whether this decrease occurred in hepatocytes, primary cells were isolated from wild‐type (WT) mice and stimulated with vehicle or PA, an inducer of lipid accumulation and IR in hepatocytes . Compared with vehicle‐treated cells, PA triggered a marked decrease in Dusp9 expression in hepatocytes (Fig.…”

FNDC5 Alleviates Hepatosteatosis by Restoring AMPK/mTOR-Mediated Autophagy, Fatty Acid Oxidation, and Lipogenesis in Mice

“…5C). Palmitate-induced lipid accumulation is generally used as a cellular steatosis model (31). To ascertain whether reduced autophagy in FNDC5 2/2 mice is involved in lipid accumulation, the effects of rapamycin and Atg5 siRNA on palmitate-induced lipid accumulation in primary hepatocytes were investigated.…”