Adipose tissue is a dynamic organ that makes critical contributions to whole body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, PPARγ is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes in vivo. Short-term PPARγ deficiency in adipocytes reduces whole body insulin sensitivity, but adipocytes are viable both in vitro and in vivo. However, after high fat diet exposure, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature adipocytes are depleted for both PPARγ and C/EBPα, they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo. Surprisingly, although thiazolidinediones (TZDs -- PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in adipocytes is not required for the whole-body insulin-sensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole body metabolic homeostasis.
- ↵*Correspondence should be addressed to: Philipp E. Scherer, Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-8549, USA, E-mail: , Tel: 214-648-8715, Fax: 214-648-8720
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