Tetrahydrocurcumin ameliorates free fatty acid-induced hepatic steatosis and improves insulin resistance in HepG2 cells.

Abstract

Elevated levels of free fatty acids (FFAs) in the liver, resulting from either increased lipolysis or imbalanced FFAs flux, is a key pathogenic factor of hepatic steatosis. This study was conducted to examine the therapeutic effect of tetrahydrocurcumin (THC), a naturally occurring curcuminoid and a metabolite of curcumin, on oleic acid (OA)-induced steatosis in human hepatocellular carcinoma cells and to elucidate the underlying mechanism. HepG2 cells were incubated with OA to induce steatosis, and then treated with various concentrations of THC. The results showed that THC treatment significantly decreased lipid accumulation in OA-treated HepG2 cells, possibly, by inhibiting the expression of the lipogenic proteins, sterol regulatory element-binding protein 1 (SREBP-1c), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4). Moreover, THC attenuated OA-induced hepatic lipogenesis in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner, which was reversed by pretreatment with an AMPK inhibitor. THC promoted lipolysis and upregulated the expression of genes involved in β-oxidation. Glucose uptake and insulin signaling impaired in HepG2 cells incubated with OA were abated by THC treatment, including phosphorylation of the insulin receptor substrate 1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Akt and downstream signaling pathways, forkhead box protein O1 (FOXO1) and glycogen synthase kinase 3 β (GSK3β), which are involved in gluconeogenesis and glycogen synthesis, respectively. Altogether, these results demonstrated the novel therapeutic benefit of THC against hepatic steatosis and, consequently, a potential treatment for non-alcoholic fatty liver disease (NAFLD).

• Authors: Jin-Wun Chen, Zwe-Ling Kong, Mei-Ling Tsai, Chih-Yu Lo, Chi-Tang Ho, Ching-Shu Lai
• Journal: Journal of food and drug analysis (J Food Drug Anal) Vol. 26 Issue 3 Pg. 1075-1085 (07 2018) ISSN: 2224-6614 [Electronic] China (Republic : 1949- )
• PMID: 29976400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• FABP4 protein, human
• Fatty Acid-Binding Proteins
• Fatty Acids, Nonesterified
• PPAR alpha
• Sterol Regulatory Element Binding Protein 1
• tetrahydrocurcumin
• Oleic Acid
• Curcumin
• Glucose

Topics

• Curcumin (analogs & derivatives, pharmacology)
• Fatty Acid-Binding Proteins (genetics, metabolism)
• Fatty Acids, Nonesterified (adverse effects)
• Fatty Liver (genetics, metabolism, physiopathology)
• Glucose (metabolism)
• Hep G2 Cells
• Humans
• Insulin Resistance
• Lipogenesis (drug effects)
• Oleic Acid (adverse effects)
• PPAR alpha (genetics, metabolism)
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)