Abstract

WY14643 combined with all-trans retinoic acid acts via p38 MAPK to induce â�?�?browningâ�? of white adipocytes in mice

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 < 0.05). WY14643 combined with t-RA was observed to induce UCP1 mRNA expression, protein expression, and phosphorylation of p38 MAPK (P < 0.05). SB203580 combined with WY14643 and t-RA suppressed UCP1 mRNA expression, protein expression, and p38 MAPK phosphorylation (P < 0.05). WY14643 combined with t-RA can induce the transformation of white adipocytes to brown adipocytes through activation of the p38 MAPK signaling pathway.

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