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Am J Physiol Endocrinol Metab (June 7, 2005). doi:10.1152/ajpendo.00010.2005
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Submitted on January 11, 2005
Accepted on May 27, 2005

Metabolic and Cellular Plasticity in White Adipose Tissue II: Role of Peroxisome Proliferator Activated Receptor Alpha

Pipeng Li1, Zhengxian Zhu1, Yuyan Lu1, and James G Granneman1*

1 Center for Integrative Metabolic and Endocrine Research, Departments of Psychiatry and Pathology, Wayne State University School of Medicine, Detroit, MI, USA

* To whom correspondence should be addressed. E-mail: jgranne{at}med.wayne.edu.

Chronic activation of adipocyte {beta}-adrenergic receptors induces remodeling of white adipose tissue (WAT) that includes a transient inflammatory response followed by mitochondrial biogenesis, induction of fatty acid oxidation genes and elevation of tissue oxidative metabolism. Gene profiling experiments of WAT during remodeling induced by the {beta}-adrenergic receptor (Adrb3) agonist CL 316,243 (CL) suggested that peroxisome proliferator activated receptor alpha (Ppara), which is upregulated by CL, might be an important transcriptional regulator of that process. Histological, physiological and molecular analysis of CL-induced remodeling in wild-type mice and mice lacking Ppara demonstrated that Ppara was important for inducing adipocyte mitochondrial biogenesis and upregulating gene involved in fatty acid oxidation. Furthermore, Ppara deficient mice exhibited sustained WAT inflammation during CL treatment, indicating that upregulation of Ppara limits proinflammatory signaling during chronic lipolytic activation. Together, these data support the hypothesis that WAT remodeling is an adaptive response to excessive fatty acid mobilization whereby Ppara and its downstream targets elevate fatty acid catabolism and suppress proinflammatory signaling.




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