title: Transcriptional activation of peroxisome proliferator-activated receptor-gamma requires activation of both protein kinase A and Akt during adipocyte differentiation.
abstract: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is required for the conversion of pre-adipocytes. However, the mechanism underlying activation of PPAR-gamma is unclear. Here we showed that cAMP-induced activation of protein kinase A (PKA) and Akt is essential for the transcriptional activation of PPAR-gamma. Hormonal induction of adipogenesis was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), by a protein kinase A (PKA) inhibitor (H89), and by a Rap1 inhibitor (GGTI-298). Transcriptional activity of PPAR-gamma was markedly enhanced by 3-isobutyl-1-methylxanthine (IBMX), but not insulin and dexamethasone. In addition, IBMX-induced PPAR-gamma transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors. 8-(4-Chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-Me-cAMP) which is a specific agonist for exchanger protein directly activated by cAMP (Epac) significantly induced the activation of Akt. Furthermore, knock-down of Akt1 markedly attenuated PPAR-gamma transcriptional activity. These results indicate that both PKA and Akt signaling pathways are required for transcriptional activation of PPAR-gamma, suggesting post-translational activation of PPAR-gamma might be critical step for adipogenic gene expression.
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Sang-pil
authors.initials: SP
authors.lastname: Kim
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ha
authors.forename: Sung Ji
authors.initials: SJ
authors.lastname: Yun
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.forename: Sung Woon
authors.initials: SW
authors.lastname: Chung
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Hong
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases