First Author | Mitterberger MC | Year | 2012 |
Journal | Exp Cell Res | Volume | 318 |
Issue | 8 | Pages | 877-86 |
PubMed ID | 22507175 | Mgi Jnum | J:183923 |
Mgi Id | MGI:5319566 | Doi | 10.1016/j.yexcr.2012.02.011 |
Citation | Mitterberger MC, et al. (2012) Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-gamma2. Exp Cell Res 318(8):877-86 |
abstractText | Carbonic anhydrase III (CAIII) is an isoenzyme of the CA family. Because of its low specific anhydrase activity, physiological functions in addition to hydrating CO(2) have been proposed. CAIII expression is highly induced in adipogenesis and CAIII is the most abundant protein in adipose tissues. The function of CAIII in both preadipocytes and adipocytes is however unknown. In the present study we demonstrate that adipogenesis is greatly increased in mouse embryonic fibroblasts (MEFs) from CAIII knockout (KO) mice, as demonstrated by a greater than 10-fold increase in the induction of fatty acid-binding protein-4 (FABP4) and increased triglyceride formation in CAIII(-/-) MEFs compared with CAIII(+/+) cells. To address the underlying mechanism, we investigated the expression of the two adipogenic key regulators, peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) and CCAAT/enhancer binding protein-alpha. We found a considerable (approximately 1000-fold) increase in the PPARgamma2 expression in the CAIII(-/-) MEFs. Furthermore, RNAi-mediated knockdown of endogenous CAIII in NIH 3T3-L1 preadipocytes resulted in a significant increase in the induction of PPARgamma2 and FABP4. When both CAIII and PPARgamma2 were knocked down, FABP4 was not induced. We conclude that down-regulation of CAIII in preadipocytes enhances adipogenesis and that CAIII is a regulator of adipogenic differentiation which acts at the level of PPARgamma2 gene expression. |