title: Human cholesteryl ester transfer protein enhances insulin-mediated glucose uptake in adipocytes.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
authors.forename: Xianxia
authors.initials: X
authors.lastname: Ju
authors.forename: Qin
authors.initials: Q
authors.lastname: Cui
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.forename: Yina
authors.initials: Y
authors.lastname: Chang
authors.forename: Kunlin
authors.initials: K
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhou
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014162:Transfection
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D047495:PPAR gamma; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose