Glucose transporter 4 (GLUT4) distribution on metabolic healthy obese (MHO) vs metabolic unhealthy obese (MUO)

Abstract

Introduction: Adipose tissue plays a crucial role in metabolic dysregulation. Several processes are involved during adipose tissue dysfunction, such as enlarged adipocytes, impaired adipocyte differentiation, inflammation, remodeling and/or fibrosis. In vitro studies and animal models have demonstrated that adipocyte hypertrophy alone is enough to impair glucose uptake, which may be explained by changes of cell distribution of Glucose transporter 4 (GLUT4) and trafficking, reflecting a new potential regulatory pathway. Obese patients can be subclassified in cardiometabolic risk phenotypes with significant difference in adipose tissue characteristics and glucose uptake. Therefore, the Glut-4 distribution in adipocytes from the so known: 1) metabolic healthy obese (MHO) and 2) metabolic unhealthy obese (MUO), may help to understand cardiometabolic risk differences between them. Aims: To analyze GLUT 4 distribution in MHO vs MUO patients. Methods: Cross-sectional observational study. Candidates for bariatric surgery were included. Patients were classified as MHO or MUO. Samples from subcutaneous (SAT) and visceral adipose tissue (VAT) were obtained during bariatric surgery, afterwards tissue. GLUT 4 expression and distribution in adipocytes was evaluated by immunofluorescence and image analysis. Results: Six patients were included (MHO n=2 and MUO n=4). According to the distribution of GLUT-4 expression within adipocyte membrane, patients with MUO phenotype showed significantly larger distance between GLUT-4 molecules, either at SAT or VAT.