2118-P: Evidence of GIP-Induced Regulation of Fatty Acid Desaturase 2 (FADS2) Gene Expression in Subcutaneous Adipose Tissue

Abstract

The incretin glucose-dependent insulinotropic polypeptide (GIP) is an important regulator of postprandial metabolism by stimulating insulin secretion and inhibiting lipolysis in the adipocytes. GIP is also involved in the development of the low-grade tissue inflammation upon high-fat and high-sucrose diet, but complete mechanisms of this action remain poorly understood. Fatty acid (FA) composition affects the obesity-associated low-grade inflammation. Recently human studies showed that fatty acid desaturase 2 (FADS2) gene polymorphism is associated with FA metabolism and adipose tissue inflammation. Here we aimed to investigate the effect on GIP infusion on the FADS2 gene expression in subcutaneous adipose tissue (SAT) and FA composition in humans. Eleven male subjects without diabetes (age: 36.9 ± 1.9 years; body mass index 32.2 ± 1.0 kg/m2) underwent saline infusion (0.9% NaCl), GIP infusion at an infusion rate of 2.0 pmol kg−1min−1, lipid infusion (Intralipid 20% emulsion for infusion) or combined GIP and lipid infusion of 4 hours duration. SAT biopsies were taken at −40 min and 240 min of infusions and FADS2 mRNA levels were detected by real-time PCR. FA compositions were measured in plasma at 0 and 240 minutes of each test by LCMS. FADS2 desaturating activity was calculated as a ratio of 18:3n-6 to 18:2n-6 FA, 20:3n-6 to 20:2n-6 FA, 22:4n-5 to 22:4n-6 FA and C22:6n-3 to C22:5n3 FA. FADS2 gene expression was increased after GIP, lipid and combined GIP and lipid infusion (p<0.01) compared to saline infusion. 18:3n-6 to 18:2n-6 FA ratio was significantly down-regulated at the end of GIP+lipid and lipid infusion but did not change after the GIP infusion alone. The observed GIP-dependent upregulation of FADS2 gene in adipose tissue may influence regulation of adipose tissue inflammation in postprandial state and in obesity. The observed down-regulation of 18:3n-6 to 18:2n-6 ratio reflects the saturation of enzyme capacity by substrate overload during the experiments Disclosure O. Ramich: None. A.F. Pfeiffer: Advisory Panel; Self; Abbott, Berlin-Chemie AG, Novo Nordisk A/S. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG, Sanofi-Aventis Deutschland GmbH. N.N. Rudovich: None.