TY - JOUR T1 - Inhibition of p38MAPK Increases Adipogenesis From Embryonic to Adult Stages JF - Diabetes JO - Diabetes SP - 281 LP - 289 DO - 10.2337/diabetes.55.02.06.db05-0963 VL - 55 IS - 2 AU - Aouadi, Myriam AU - Laurent, Kathiane AU - Prot, Matthieu AU - Le Marchand-Brustel, Yannick AU - Binétruy, Bernard AU - Bost, Frédéric Y1 - 2006/02/01 UR - http://diabetes.diabetesjournals.org/content/55/2/281.abstract N2 - Formation of new adipocytes from precursor cells contributes to adipose tissue expansion and obesity. In this study, we asked whether p38 mitogen-activated protein kinase (MAPK) pathway regulates normal and pathological adipogenesis. In both dietary and genetically (ob/ob) obese mice, adipose tissues displayed a marked decrease in p38MAPK activity compared with the same tissues from lean mice. Furthermore, p38MAPK activity was significantly higher in preadipocytes than in adipocytes, suggesting that p38MAPK activity decreases during adipocyte differentiation. In agreement with an inhibitory role of p38MAPK in this process, we found that in vitro inhibition of p38MAPK, with the specific inhibitor PD169316, increased the expression of adipocyte markers in several cellular models, from embryonic to adult stages. Importantly, the expression of adipocyte markers was higher in p38MAPKα knockout cells than in their wild-type counterparts. Phosphorylation of C/EBPβ, which enhances its transcriptional activity, is increased after p38MAPK inhibition. Finally, either inhibition or disruption of p38MAPK increased peroxisome proliferator–activated receptor (PPAR)γ expression and transactivation. Rescue of p38MAPK in knockout cells reduced PPARγ activity to the low basal level of wild-type cells. We demonstrate here, by using multipronged approaches involving p38 chemical inhibitor and p38MAPKα knockout cells, that p38MAPK plays a negative role in adipogenesis via inhibition of C/EBPβ and PPARγ transcriptional activities. ER -