title: Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-γ2.
abstract: 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-γ2 (PPARγ2) and CCAAT/enhancer binding protein-α. We found a considerable (approximately 1000-fold) increase in the PPARγ2 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 PPARγ2 and FABP4. When both CAIII and PPARγ2 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 PPARγ2 gene expression.
authors.affiliation: Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Austria.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mitterberger
authors.forename: Geumsoo
authors.initials: G
authors.lastname: Kim
authors.forename: Ursula
authors.initials: U
authors.lastname: Rostek
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Levine
authors.forename: Werner
authors.initials: W
authors.lastname: Zwerschke
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis; D024403:Carbonic Anhydrase III / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004622:Embryo, Mammalian; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D014280:Triglycerides; D024403:Carbonic Anhydrase III