Metabolic and Steatohepatitis
Compound K modulates fatty acid-induced lipid droplet formation and expression of proteins involved in lipid metabolism in hepatocytes
Version of Record online: 2 SEP 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 33, Issue 10, pages 1583–1593, November 2013
How to Cite
Liver Int. 2013; 33: 1583–1593
- Issue online: 6 OCT 2013
- Version of Record online: 2 SEP 2013
- Accepted manuscript online: 19 AUG 2013 06:13AM EST
- Manuscript Accepted: 24 JUL 2013
- Manuscript Received: 6 AUG 2012
- National Institute of Complementary Medicine
- National Health and Research Council of Australia. Grant Numbers: 632630, 1049857
- Sydney Medical Foundation
- 5′-AMP-activated protein kinase;
- acyl-CoA oxidase 1;
- Compound K;
- ginsenoside metabolite;
- hepatic steatosis;
- lipid droplets;
- non-alcoholic fatty liver disease;
- peroxisome proliferator-activated receptor-α
Background & Aims
A key factor in the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) is hepatic steatosis. Incubation of human hepatic cells with free fatty acids (FFAs) causes accumulation of neutral lipids in lipid droplets (LDs) and serves as a model for hepatic steatosis. Ginsenosides, active constituents of ginsengs, have demonstrated beneficial effects in various pharmacological areas, including diabetes, however their effect on lipid accumulation in hepatocytes remains unclear. Here, we examine the effect of compound K (ComK), an active metabolite of ginsenosides, on the regulation of LD formation and on the expression of proteins involved in lipid homeostasis in hepatocytes.
HuH7 cells were pretreated with ComK, followed by lipid loading with FFA. LDs were visualized using Oil Red O staining and immunohistochemistry for the LD-related protein PLIN2. Triglyceride levels were determined in isolated LDs. The expression of proteins involved in lipid homeostasis was examined by Western blotting.
Treatment with ComK significantly decreased LD formation in FFA-loaded HuH7 cells and increased phosphorylation levels of AMPK, and its substrate ACC. ComK also increased protein expression of peroxisome proliferator-activated receptor-α (PPAR-α) and acyl-CoA oxidase (ACOX1) together with elevated activity of a PPAR-α response element reporter construct. These effects were inhibited by the PPAR-α antagonist MK886.
ComK reduced LD formation and TG accumulation in FFA-loaded hepatocytes, in part by up-regulating AMPK activity and PPAR-α related pathways. These results suggest that ComK may have efficacy for the treatment of hepatic steatosis and associated diseases.