The Antagonist Effect of Arachidonic Acid on GLUT4 Gene Expression by Nuclear Receptor Type II Regulation

Objectives: Obesity is a complex disease that has a strong association with diet and lifestyle. Dietary factors can influence the expression of key genes connected to insulin resistance, lipid metabolism, and adipose tissue composition. In this study, our objective was to determine gene expression and fatty acid (FA) profiles in visceral adipose tissue (VAT) from lean and morbidly obese individuals. We also aimed to study the agonist effect of dietary factors on glucose metabolism. Design and methods: Lean and low and high insulin resistance morbidly obese subjects (LIR-MO and HIR-MO) were included in this study. The gene expression of liver X receptor type alpha (LXR-α) and glucose transporter type 4 (GLUT4) and the FA profiles in VAT were determined. Additionally, the in vivo and in vitro agonist effects of oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) by peroxisome proliferator-activated receptor type gamma 2 (PPAR-γ2) on the activity of GLUT4 were studied. Results: Our results showed a dysregulation of GLUT4 and LXR-α in VAT of morbidly obese subjects. In addition, a specific FA profile for morbidly obese individuals was found. Finally, AA was an PPAR-γ2 agonist that activates the expression of GLUT4. Conclusions: Our study suggests a dysregulation of LXR-α and GLUT4 expression in VAT of morbidly obese individuals. FA profiles in VAT could elucidate their possible role in lipolysis and adipogenesis. Finally, AA binds to PPAR-γ2 to activate the expression of GLUT4 in the HepG2 cell line, showing an alternative insulin-independent activation of GLUT4.