Serum Levels of Retinol Binding Protein 4 (RBP4) and Adipose Tissue Expression Levels of Protein Tyrosine Phosphatase 1B (PTP1B) are Increased in Obese Men Resident in North East of Scotland Without Any Changes in Endoplasmic Reticulum (ER) Stress Response Marker Genes

Background: Retinol-binding protein 4 (RBP4) is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B) expression levels, as well as other genes involved in the endoplasmic-reticulum (ER) stress response, are increased in adipose tissue of obese, high-fat diet fed mice. In this study, we investigated if serum- and/or adipose-tissue RBP4 protein levels, and expression levels of PTP1B and other ER stress-response genes, are altered in obese and obese/diabetic men resident in North East of Scotland. Methods: We studied three groups of male volunteers: 1) normal/overweight (body mass index (BMI) 30) and 3) obese/diabetic group (BMI>30) controlling their diabetes either by diet or anti-diabetic drug, metformin. We analysed their serum- and adipose-tissue RBP4 protein levels, as well as adipose tissue mRNA expression of PTP1B, BIP (binding immunoglobulinprotein), ATF4 (activated transcription factor 4) and GRP94 (glucose-regulated protein 94), alongside other markers of adiposity (% body fat, leptin, cholesterol, triglycerides) and insulin resistance (oral glucose tolerance tests (OGTT), insulin, HOMA-IR, C-reactive protein (CRP), adiponectin). Results: We found that obese Scottish subjects had significantly higher serum-RBP4 protein levels in comparison to the normal/overweight subjects (p<0.01). Serum-RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (p<0.05). Adipose-tissue RBP4 protein levels were comparable between all three groups of subjects and so were serum- and adipose-transthyretin (TTR) levels. Adipose-tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (p