Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARγ-dependent autocrine mechanism

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Wayne State University

Details

Original languageEnglish (US)
Pages (from-to)H690-H698
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number3
StatusPublished - Sep 1 2010
Peer-reviewedYes

Abstract

In experimental animal and cell culture models, activation of peroxisome proliferator-activated receptor (PPAR) γ in heart has been shown to have beneficial effects on cardiac function and cardiomyocyte physiology. The goal of this study was to identify the signaling pathway by which PPARγ activation protects cardiomyocytes from the deleterious effects of hypertrophic stimuli. In primary cardiomyocyte cultures, we found that genetic or pharmacological activation of PPARγ protected cells from cardiac hypertrophy induced by α-adrenergic stimulation. Examination of gene expression in these cells revealed a surprising increase in the expression of adiponectin in cardiomyocytes and secretion of the high-molecular-weight form of the hormone into media. Using RNAi to block PPARγ-induced adiponectin production or adiponectin receptor gene expression, we found that the PPARγ-mediated antihypertrophic effect required cardiomyocyte-produced adiponectin, as well as an intact adiponectin signaling pathway. Furthermore, mice expressing constitutive-active PPARγ and cardiomyocyte specific adiponectin expression were protected from high-fat diet-induced cardiac hypertrophy and remodeling. These findings demonstrate that functional adiponectin hormone can be produced from the heart and raise the possibility that beneficial effects of PPARγ activation in heart could be due in part to local production of adiponectin that acts on cardiomyocytes in an autocrine manner.

    Research areas

  • Adiponectin, Cardiac hypertrophy, Peroxisome proliferator-activated receptor γ, Regulation of gene expression, Thiazolidinediones, Type 2 diabetes

Citation formats

APA

Amin, R. H., Mathews, S. T., Alli, A., & Leff, T. (2010). Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARγ-dependent autocrine mechanism. American Journal of Physiology - Heart and Circulatory Physiology, 299(3), H690-H698. https://doi.org/10.1152/ajpheart.01032.2009

Harvard

Amin, RH, Mathews, ST, Alli, A & Leff, T 2010, 'Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARγ-dependent autocrine mechanism', American Journal of Physiology - Heart and Circulatory Physiology, vol. 299, no. 3, pp. H690-H698. https://doi.org/10.1152/ajpheart.01032.2009