title: WY14643 combined with all-trans retinoic acid acts via p38 MAPK to induce "browning" of white adipocytes in mice.
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 peroxi-some 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 "brown-ing" using western blot. All concentrations of WY14643 failed to in-duce 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 phosphory-lation 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.
authors.affiliation: Department of Endocrinology and Metabolism, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: G J
authors.initials: GJ
authors.lastname: Sun
authors.affiliation: Department of Obstetrics, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: J X
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Endocrinology and Metabolism, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: H R
authors.initials: HR
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China shoujunwangcn@163.com.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004357:Drug Synergism; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D011725:Pyridines; D011743:Pyrimidines; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014212:Tretinoin; C006253:pirinixic acid; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580