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

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.

PLTP secreted by HepG2 cells resembles the high-activity PLTP form in human plasma

“…The HepG2 cell system is a relevant model with regard to human hepatic fatty acid uptake, lipid synthesis, apolipoprotein synthesis, and lipolytic enzyme and transfer protein synthesis (LCAT, hepatic lipase, cholesteryl ester transfer protein), as well as apoB-100-lipoprotein assembly and secretion (31,36). While this study supports the previous findings that PLTP activity accumulates in the culture medium of HepG2 cells (37,38), no detailed characterization of the secreted PLTP has been carried out before.…”

Leptin inhibits apolipoprotein M transcription and secretion in human hepatoma cell line, HepG2 cells

“…In the present study, we investigated the effects of leptin on the transcription and secretion of apoM in HepG2 cells. We chose HepG2 cells as these cells have a known leptin receptor [8]. Also, the HepG2 cells can synthesize and secrete lipoprotein including very lower density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and HDL, as well as a variety of plasma apolipoproteins including apoB, apoE, apoAs, apoCs and apoM.…”

PLTP activity decreases with weight loss

“…The change in PLTP was not correlated with the change in HL, LPL, TG, or fasting insulin. The relationship with leptin was also investigated, because leptin is produced mainly in SQF (20) and has been reported to be correlated with PLTP in humans (13) or to be related to a decrease in PLTP mRNA in HepG2 cells (32). In the present study, the change in leptin was not associated with the change in PLTP activity, despite the fact that leptin demonstrated associations similar to those observed for PLTP, being positively correlated with the change in SQF (r ϭ 0.67, P ϭ 0.002) and change in FM (r ϭ 0.51, P ϭ 0.036), but not associated with the change in IAF (r ϭ 0.23, P ϭ 0.35) or S I (r ϭ Ϫ0.27, P ϭ 0.26).…”