Dataset Information

Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor ? in Adipogenesis.

ABSTRACT: Much of our knowledge on adipogenesis comes from cell culture models of preadipocyte differentiation. Adipogenesis is induced by treating confluent preadipocytes with the adipogenic cocktail, which activates transcription factors (TFs) glucocorticoid receptor (GR) and CREB within minutes and increases expression of TFs C/EBP?, C/EBP?, KLF4, and Krox20 within hours. All of these TFs have been shown to be capable of promoting adipogenesis in culture when they are overexpressed. However, it has remained unclear whether endogenous KLF4 and Krox20 are required for adipogenesis in culture and in vivo Using conditional knockout mice and derived white and brown preadipocytes, we show that endogenous KLF4 and Krox20 are dispensable for adipogenesis in culture and for brown adipose tissue development in mice. In contrast, the master adipogenic TF peroxisome proliferator-activated receptor ? (PPAR?) is essential. These results challenge the existing model on transcriptional regulation in the early phase of adipogenesis and highlight the need of studying adipogenesis in vivo.

SUBMITTER: Park YK

PROVIDER: S-EPMC5214852 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor γ in Adipogenesis.

Park Young-Kwon YK Wang Limin L Giampietro Anne A Lai Binbin B Lee Ji-Eun JE Ge Kai K

Molecular and cellular biology 20170104 2

Much of our knowledge on adipogenesis comes from cell culture models of preadipocyte differentiation. Adipogenesis is induced by treating confluent preadipocytes with the adipogenic cocktail, which activates transcription factors (TFs) glucocorticoid receptor (GR) and CREB within minutes and increases expression of TFs C/EBPβ, C/EBPδ, KLF4, and Krox20 within hours. All of these TFs have been shown to be capable of promoting adipogenesis in culture when they are overexpressed. However, it has rem ...[more]

PMID: 27777310

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Project description:ObjectiveCardiac fibrosis is an important component of diabetic cardiomyopathy. Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands repress proinflammatory gene expression, including that of osteopontin, a known contributor to the development of myocardial fibrosis. We thus investigated the hypothesis that PPARgamma ligands could attenuate cardiac fibrosis.Research design and methodsWild-type cardiomyocyte- and macrophage-specific PPARgamma(-/-) mice were infused with angiotensin II (AngII) to promote cardiac fibrosis and treated with the PPARgamma ligand pioglitazone to determine the roles of cardiomyocyte and macrophage PPARgamma in cardiac fibrosis.ResultsCardiomyocyte-specific PPARgamma(-/-) mice (cPPARgamma(-/-)) developed spontaneous cardiac hypertrophy with increased ventricular osteopontin expression and macrophage content, which were exacerbated by AngII infusion. Pioglitazone attenuated AngII-induced fibrosis, macrophage accumulation, and osteopontin expression in both wild-type and cPPARgamma(-/-) mice but induced hypertrophy in a PPARgamma-dependent manner. We pursued two mechanisms to explain the antifibrotic cardiomyocyte-PPARgamma-independent effects of pioglitazone: increased adiponectin expression and attenuation of proinflammatory macrophage activity. Adenovirus-expressed adiponectin had no effect on cardiac fibrosis and the PPARgamma ligand pioglitazone did not attenuate AngII-induced cardiac fibrosis, osteopontin expression, or macrophage accumulation in monocyte-specific PPARgamma(-/-) mice.ConclusionsWe arrived at the following conclusions: 1) both cardiomyocyte-specific PPARgamma deficiency and activation promote cardiac hypertrophy, 2) both cardiomyocyte and monocyte PPARgamma regulate cardiac macrophage infiltration, 3) inflammation is a key mediator of AngII-induced cardiac fibrosis, 4) macrophage PPARgamma activation prevents myocardial macrophage accumulation, and 5) PPARgamma ligands attenuate AngII-induced cardiac fibrosis by inhibiting myocardial macrophage infiltration. These observations have important implications for potential interventions to prevent cardiac fibrosis.

Dataset Information

Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor ? in Adipogenesis.

Publications

Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor γ in Adipogenesis.

Similar Datasets

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