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

AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer pr otein (CETP) are key enzymes in lipoprotein metabolism facilitating the tra nsfer and exchange of cholesteryl esters, triglycerides and phospholipids b etween lipoproteins. In the study presented here, we investigated the influ ence of two hormones-the adipocyte-derived hormone leptin as well as insuli n on the hepatic secretion of both, PLTP and CETP METHODS: PLTP activity and CETP concentration-measured by exogenous substra te assay and enzyme-linked immunosorbent assay-were determined in supernata nt of human hepatoma cell line HepG2 after single or combined exposure to l eptin and insulin at physiological and supraphysiological concentrations, r espectively. 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 exposur e 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 c ounteracting the potentially harmful action of lipid transfer proteins, par ticularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resi stance.