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Nat Med. 2013 May;19(5):557-66. doi: 10.1038/nm.3159. Epub 2013 May 7.

PPARγ signaling and metabolism: the good, the bad and the future.

Author information

1
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.

Abstract

Thiazolidinediones (TZDs) are potent insulin sensitizers that act through the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) and are highly effective oral medications for type 2 diabetes. However, their unique benefits are shadowed by the risk for fluid retention, weight gain, bone loss and congestive heart failure. This raises the question as to whether it is possible to build a safer generation of PPARγ-specific drugs that evoke fewer side effects while preserving insulin-sensitizing potential. Recent studies that have supported the continuing physiologic and therapeutic relevance of the PPARγ pathway also provide opportunities to develop newer classes of molecules that reduce or eliminate adverse effects. This review highlights key advances in understanding PPARγ signaling in energy homeostasis and metabolic disease and also provides new explanations for adverse events linked to TZD-based therapy.

PMID:
23652116
PMCID:
PMC3870016
DOI:
10.1038/nm.3159
[Indexed for MEDLINE]
Free PMC Article

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