Research Article

WY14643 combined with all-trans retinoic acid acts via p38 MAPK to induce “browning” of white adipocytes in mice

Published: June 26, 2015
Genet. Mol. Res. 14 (2) : 6978-6984 DOI: 10.4238/2015.June.26.6

Abstract

The ability of mammals to resist body fat accumulation is linked to their ability to expand the number of “brown adipocytes” within white fat depots. All-trans retinoic acid (t-RA) and peroxi­some proliferator-activated receptor-α (PPARα) have been implicated in “browning-like” or “browning” programs, respectively. However, a PPARα-agonist (WY14643) failed to regulate the expression of the uncoupling protein 1(UCP1) gene unless combined with retinoic acid. This study investigated the effects of the PPARα-agonist WY14643 combined with t-RA, on the “browning” of white adipocytes in mice mediated by UCP1, and the molecular mechanisms involved in this process. We compared the effects of WY14643 alone and WY14643 combined with t-RA or the p38 MAPK-inhibitor, SB203580, on white adipocytes after 24 h using the expression of UCP1, detected with RT-PCR and western blot. We also determined the mechanism by which p38 MAPK and phospho-p38 MAPK influence the process of “brown­ing” using western blot. All concentrations of WY14643 failed to in­duce UCP1 mRNA expression, protein expression, or phosphorylation of p38 MAPK (P

The ability of mammals to resist body fat accumulation is linked to their ability to expand the number of “brown adipocytes” within white fat depots. All-trans retinoic acid (t-RA) and peroxi­some proliferator-activated receptor-α (PPARα) have been implicated in “browning-like” or “browning” programs, respectively. However, a PPARα-agonist (WY14643) failed to regulate the expression of the uncoupling protein 1(UCP1) gene unless combined with retinoic acid. This study investigated the effects of the PPARα-agonist WY14643 combined with t-RA, on the “browning” of white adipocytes in mice mediated by UCP1, and the molecular mechanisms involved in this process. We compared the effects of WY14643 alone and WY14643 combined with t-RA or the p38 MAPK-inhibitor, SB203580, on white adipocytes after 24 h using the expression of UCP1, detected with RT-PCR and western blot. We also determined the mechanism by which p38 MAPK and phospho-p38 MAPK influence the process of “brown­ing” using western blot. All concentrations of WY14643 failed to in­duce UCP1 mRNA expression, protein expression, or phosphorylation of p38 MAPK (P