title: EGF receptor (ERBB1) abundance in adipose tissue is reduced in insulin-resistant and type 2 diabetic women.
abstract: BACKGROUND
  Indications of adipose tissue dysfunction correlate with systemic insulin resistance and type 2 diabetes. It has been suggested that a defect in adipose tissue turnover may be involved in the development of these disorders. Whether this dysfunction causes or exacerbates systemic insulin resistance is not fully understood. OBJECTIVES, PARTICIPANTS, AND MEASURES: We tested whether the expression of members of the mitogenic ErbB family was reduced in adipose tissue of insulin-resistant individuals and whether ErbB1 and ErbB2 were involved in adipogenesis. Thirty-two women covering a wide range of body mass index values and insulin sensitivity participated in the cross-sectional portion of this study. We also studied preadipocytes isolated from 12 insulin-sensitive individuals to evaluate the impact of ErbB1 or ErbB2 inhibition on adipogenesis in vitro. For this purpose, we measured phospho-ErbB1 and phospho-ErbB2 levels using ELISA and the expression of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ-regulated genes by real-time PCR.
  
  
  RESULTS
  Among the ErbB family members, only ErbB1 expression was correlated with insulin sensitivity. Additionally, ErbB1 levels correlated positively with PPARγ and several PPARγ-regulated genes including acyl-coenzyme A synthetase long-chain family member 1 (ACSL1), adiponectin, adipose tissue triacylglycerol lipase (ATGL), diacylglycerol acyl transferase 1 (DGAT1), glycerol-3-phosphate dehydrogenase 1 (GPD1), and lipoprotein lipase (LPL), but negatively with CD36 and fatty acid-binding protein 4 (FABP4). In preadipocyte culture, ErbB1, but not ErbB2, inhibition was associated with a reduction in the expression of all the above-mentioned genes.
  
  
  CONCLUSIONS
  These findings demonstrate a key role for ErbB1 in adipogenesis and suggest that lower ErbB1 protein abundance may lead to adipose tissue dysfunction.
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
authors.forename: Carlyle
authors.initials: C
authors.lastname: Rogers
authors.forename: Fatiha
authors.initials: F
authors.lastname: Moukdar
authors.forename: Marie A
authors.initials: MA
authors.lastname: McGee
authors.forename: Barbara
authors.initials: B
authors.lastname: Davis
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Buehrer
authors.forename: Kiefer W
authors.initials: KW
authors.lastname: Daniel
authors.forename: Sheila
authors.initials: S
authors.lastname: Collins
authors.forename: Hisham
authors.initials: H
authors.lastname: Barakat
authors.forename: Jacques
authors.initials: J
authors.lastname: Robidoux
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015992:Body Mass Index; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D047495:PPAR gamma; D066246:ErbB Receptors; D008071:Lipoprotein Lipase