EGF Receptor (ERBB1) Abundance in Adipose Tissue Is Reduced in Insulin-Resistant and Type 2 Diabetic Women

Context: 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 gamma (PPAR gamma) and PPAR gamma-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 PPAR gamma and several PPAR gamma-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. (J Clin Endocrinol Metab 97: E329-E340, 2012)