title: Retinol-binding protein 4 (RBP4) protein expression is increased in omental adipose tissue of severely obese patients.
abstract: Visceral fat has been linked to insulin resistance and type 2 diabetes mellitus (T2DM); and emerging data links RBP4 gene expression in adipose tissue with insulin resistance. In this study, we examined RBP4 protein expression in omental adipose tissue obtained from 24 severely obese patients undergoing bariatric surgery, and 10 lean controls (4 males/6 females, BMI = 23.2 +/- 1.5 kg/m(2)) undergoing elective abdominal surgeries. Twelve of the obese patients had T2DM (2 males/10 females, BMI: 44.7 +/- 1.5 kg/m(2)) and 12 had normal glucose tolerance (NGT: 4 males/8 females, BMI: 47.6 +/- 1.9 kg/m(2)). Adipose RBP4, glucose transport protein-4 (GLUT4), and p85 protein expression were determined by western blot. Blood samples from the bariatric patients were analyzed for serum RBP4, total cholesterol, triglycerides, and glucose. Adipose RBP4 protein expression (NGT: 11.0 +/- 0.6; T2DM: 11.8 +/- 0.7; lean: 8.7 +/- 0.8 arbitrary units) was significantly increased in both NGT (P = 0.03) and T2DM (P = 0.005), compared to lean controls. GLUT4 protein was decreased in both NGT (P = 0.02) and T2DM (P = 0.03), and p85 expression was increased in T2DM subjects, compared to NGT (P = 0.03) and lean controls (P = 0.003). Regression analysis showed a strong correlation between adipose RBP4 protein and BMI for all subjects, as well as between adipose RBP4 and fasting glucose levels in T2DM subjects (r = 0.76, P = 0.004). Further, in T2DM, serum RBP4 was correlated with p85 expression (r = 0.68, P = 0.01), and adipose RBP4 protein trended toward an association with p85 protein (r = 0.55, P = 0.06). These data suggest that RBP4 may regulate adiposity, and p85 expression in obese-T2DM, thus providing a link to impaired insulin signaling and diabetes in severely obese patients.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Kelly
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Kashyap
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.forename: Jennifer
authors.initials: J
authors.lastname: Major
authors.forename: Philip R
authors.initials: PR
authors.lastname: Schauer
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D050154:Adiposity / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D009852:Omentum; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma