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Compound K modulates fatty acid-induced lipid droplet formation and expression of proteins involved in lipid metabolism in hepatocytes.
Liver Int. 2013 Nov; 33(10):1583-93.LI

Abstract

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23998390

Citation

Kim, Moon-Sun, et al. "Compound K Modulates Fatty Acid-induced Lipid Droplet Formation and Expression of Proteins Involved in Lipid Metabolism in Hepatocytes." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 33, no. 10, 2013, pp. 1583-93.
Kim MS, Lee KT, Iseli TJ, et al. Compound K modulates fatty acid-induced lipid droplet formation and expression of proteins involved in lipid metabolism in hepatocytes. Liver Int. 2013;33(10):1583-93.
Kim, M. S., Lee, K. T., Iseli, T. J., Hoy, A. J., George, J., Grewal, T., & Roufogalis, B. D. (2013). Compound K modulates fatty acid-induced lipid droplet formation and expression of proteins involved in lipid metabolism in hepatocytes. Liver International : Official Journal of the International Association for the Study of the Liver, 33(10), 1583-93. https://doi.org/10.1111/liv.12287
Kim MS, et al. Compound K Modulates Fatty Acid-induced Lipid Droplet Formation and Expression of Proteins Involved in Lipid Metabolism in Hepatocytes. Liver Int. 2013;33(10):1583-93. PubMed PMID: 23998390.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compound K modulates fatty acid-induced lipid droplet formation and expression of proteins involved in lipid metabolism in hepatocytes. AU - Kim,Moon-Sun, AU - Lee,Kyoung-Tae, AU - Iseli,Tristan J, AU - Hoy,Andrew J, AU - George,Jacob, AU - Grewal,Thomas, AU - Roufogalis,Basil D, Y1 - 2013/09/02/ PY - 2012/08/06/received PY - 2013/07/24/accepted PY - 2013/9/4/entrez PY - 2013/9/4/pubmed PY - 2014/5/20/medline KW - 5′-AMP-activated protein kinase KW - Compound K KW - acyl-CoA oxidase 1 KW - ginsenoside metabolite KW - hepatic steatosis KW - lipid droplets KW - non-alcoholic fatty liver disease KW - peroxisome proliferator-activated receptor-α SP - 1583 EP - 93 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int VL - 33 IS - 10 N2 - 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1478-3231 UR - https://www.unboundmedicine.com/medline/citation/23998390/Compound_K_modulates_fatty_acid_induced_lipid_droplet_formation_and_expression_of_proteins_involved_in_lipid_metabolism_in_hepatocytes_ L2 - https://doi.org/10.1111/liv.12287 DB - PRIME DP - Unbound Medicine ER -