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Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2

International Journal of Obesity volume 25, pages 1633–1639 (2001)Cite this article

Abstract

AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism facilitating the transfer and exchange of cholesteryl esters, triglycerides and phospholipids between lipoproteins. In the study presented here, we investigated the influence of two hormones—the adipocyte-derived hormone leptin as well as insulin on the hepatic secretion of both, PLTP and CETP.

METHODS: PLTP activity and CETP concentration—measured by exogenous substrate assay and enzyme-linked immunosorbent assay—were determined in supernatant of human hepatoma cell line HepG2 after single or combined exposure to leptin and insulin at physiological and supraphysiological concentrations, respectively. Messenger-RNA of PLTP and CETP was quantified by Northern blot analysis.

RESULTS: Leptin suppressed PLTP activity and CETP-concentration by up to 33% and 23%, respectively. Insulin also suppressed PLTP activity by up to 11% and CETP-concentration by up to 16%. In combination, the two hormones had additive suppressive effects for both, PLTP activity and CETP-concentration. Northern blot analysis showed no difference in m-RNA levels after exposure to leptin or insulin.

CONCLUSIONS: Leptin and insulin, both known to increase with body fat mass, suppress production of PLTP and CETP in HepG2 cells. When extrapolated to the in vivo situation, this suppressive effect may constitute a mechanism counteracting the potentially harmful action of lipid transfer proteins, particularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resistance.

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Acknowledgements

The authors wish to thank Ronald W Clark (Department of Cardiovascular and Metabolic Diseases, Pfizer Inc.) for kindly providing the monoclonal anti CETP antibody, Professor Gunilla Olivecrona (Department of Medical Biochemistry and Biophysics, University of Umea, Sweden) for kindly providing the anti hepatic lipase antibody, and Dr Heinz Zoller (Department of Internal Medicine, University of Innsbruck) for kindly providing the plasmid containing the cDNA of GAPDH. This work was supported by grant P 11693-Med of the Austrian FWF (to JR Patsch), and by grant Nr. 6442 of the Österreichische Nationalbank (to JR Patsch).

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  1. Department of Medicine, University of Innsbruck, Innsbruck, Austria

    S Kaser, B Föger, CF Ebenbichler, R Kirchmair, R Gander, A Ritsch, A Sandhofer & JR Patsch

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  1. S Kaser
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Correspondence to JR Patsch.

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Kaser, S., Föger, B., Ebenbichler, C. et al. Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2. Int J Obes 25, 1633–1639 (2001). https://doi.org/10.1038/sj.ijo.0801807

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