Title

PPARγ: a circadian transcription factor in adipogenesis and osteogenesis.

Document Type

Article

Publication Date

11-1-2010

Institution/Department

Center for Clinical and Translational Research, Maine Medical Center Research Institute

Journal Title

Nat Rev Endocrinol

MeSH Headings

Adipogenesis, Adipose Tissue, Animals, Circadian Rhythm, Gene Expression Regulation, Humans, Liver, Mice, Muscle, Skeletal, Nuclear Proteins, Osteogenesis, Osteoporosis, PPAR gamma, Thiazolidinediones, Transcription Factors

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a critical factor for adipogenesis and glucose metabolism, but accumulating evidence demonstrates the involvement of PPARγ in skeletal metabolism as well. PPARγ agonists, the thiazolidinediones, have been widely used for the treatment of type 2 diabetes mellitus owing to their effectiveness in lowering blood glucose levels. However, the use of thiazolidinediones has been associated with bone loss and fractures. Thiazolidinedione-induced alterations in the bone marrow milieu-that is, increased bone marrow adiposity with suppression of osteogenesis-could partially explain the pathogenesis of drug-induced bone loss. Furthermore, several lines of evidence place PPARγ at the center of a regulatory loop between circadian networks and metabolic output. PPARγ exhibits a circadian expression pattern that is magnified by consumption of a high-fat diet. One gene with circadian regulation in peripheral tissues, nocturnin, has been shown to enhance PPARγ activity. Importantly, mice deficient in nocturnin are protected from diet-induced obesity, exhibit impaired circadian expression of PPARγ and have increased bone mass. This Review focuses on new findings regarding the role of PPARγ in adipose tissue and skeletal metabolism and summarizes the emerging role of PPARγ as an integral part of a complex circadian regulatory system that modulates food storage, energy consumption and skeletal metabolism.

ISSN

1759-5037

First Page

629

Last Page

636

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