Role of LXR alpha in regulating expression of glucose transporter 4 inadipocytes - Investigation on improvement of health of diabetic patients

Abstract

Background: The insulin-responsive glucose transporter 4 (GLUT4) plays prominent role in insulinmediated facilitated glucose uptake into most of the cell types, majorly muscle, liver and adipose tissue. Impaired expression of GLUT4 has been linked to insulin resistance and diabetes. In adipocytes, excesslipids that are generated from liver and by de novo lipogenesis utilizing blood sugar, are stored. There arevarious nuclear factors, co-factors and signaling mechanisms that directly and indirectly regulate glucosetransporter activity in adipocytes. Molecular mechanism behind the regulation of GLUT4 in adipocyteshas not elucidated well. Objective: Therefore, the present study focuses to explore the role of Liver X receptor- alpha (LXR alpha) onGLUT4 expression and the possible co-factors involved during in vitro adipogenesis and is assessed bymodulating the activity of LXR alpha with specific agonist and antagonist ligands in 3T3L1 differentiated cells. Results: The results demonstrate that SR 9238 (300 nM), a strong inhibitor of LXR alpha, decreased the rateof adipogenesis through reduced lipid droplet formation in adipocytes without affecting the cell morphology. The FMOC-l-Leucine (FLL), a known partial ligand of PPAR alpha, enhanced the expression of LXR alpha. Thus, it can be concluded that LXR alpha has a significant role in adipocyte differentiation and FLL interaction promoted the transcription of LXR alpha, thereby promotes GLUT4 expression. The results in this studyidentified the role of LXR alpha in regulating the expression of GLUT4 through SRC1. Conclusion: The study is of much relevance in treatment of diabetes and also opens the possibility ofidentifying new drug molecules that target LXR alpha. (c) 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz Universityfor Health Sciences. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).