Mechanisms
CETP enhances insulin-stimulated glucose uptake in human adipocyte cells (Life Sci 2011)
Original title: Human cholesteryl ester transfer protein enhances insulin-mediated glucose uptake in adipocytes
Since mouse 3T3-L1 preadipocytes do not naturally express CETP, researchers created a stable cell line expressing human CETP by transfection, then differentiated the cells into mature adipocytes to study CETP's role in insulin responses. Stable human CETP expression significantly increased total and free cholesterol in mature adipocytes without affecting PPAR-gamma or GLUT4 expression during differentiation. Upon insulin stimulation, CETP-expressing cells showed significantly higher Akt phosphorylation and glucose uptake than control cells or unmodified 3T3-L1 cells. The findings show human CETP expression raises cellular cholesterol and enhances insulin-stimulated Akt signalling and glucose uptake in adipocytes, suggesting CETP may modulate glucose metabolism and insulin action beyond its established role in lipoprotein metabolism.
Original abstract
Aims: Adipose tissue plays an important role in the pathogenesis of insulin resistance, obesity, and Type-2 diabetes. Human adipocytes express abundant cholesteryl ester transfer protein (CETP). However, the function and role of CETP in regulating lipoprotein metabolism are mostly unknown. In this study, we examined whether CETP affected the insulin-mediated responses in adipocytes.
Main Methods: Because mouse 3T3-L1 preadipocytes do not express CETP, we established a stable cell line expressing human CETP by transfecting the cells with pcDNA3.1/human CETP. We used a standard approach to differentiate the cells into mature adipocytes, and we examined the cholesterol balance and insulin responses.
Key Findings: The human CETP stable cell line expressed stable levels of CETP without affecting the expression of either peroxisome proliferator-activated receptor-gamma (PPARγ) or glucose transporter-4 (GLUT4) throughout cell differentiation. CETP expression significantly increased the level of both total and free cholesterol in the mature adipocytes. Upon insulin stimulation, CETP expressing cells had significantly higher protein kinase B (Akt) phosphorylation and 2-(3)H-deoxyglucose uptake, as compared with 3T3-L1 cells and cells transfected with control vector.
Significance: Human CETP expression increased cellular cholesterol levels and enhanced insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes. Thus, CETP may modulate glucose metabolism and insulin action in addition to its effects on lipoprotein metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.