PPARgamma activation in adipocytes is sufficient for systemic insulin sensitization.

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Sugii S, Olson P, Sears DD, Saberi M, Atkins AR, Barish GD, Hong SH, Castro GL, Yin YQ, Nelson MC, Hsiao G, Greaves DR, Downes M, Yu RT, Olefsky JM, Evans RM

PPARgamma activation in adipocytes is sufficient for systemic insulin sensitization.

Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22504-9. doi: 10.1073/pnas.0912487106. Epub 2009 Dec 16.

PubMed ID

20018750 [ View in PubMed

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Abstract

Although peroxisome proliferator-activated receptor gamma (PPARgamma) agonists such as thiazolidinediones (TZDs) are widely used to treat type 2 diabetes, how its activation in individual tissues contributes to TZD's therapeutic action remains controversial. As TZDs are known to have receptor-independent effects, we sought to establish gain-of-function animal models to delineate the receptor's insulin-sensitizing actions. Unexpectedly, we find that selective activation of PPARgamma in adipocytes, but not in macrophages, is sufficient for whole-body insulin sensitization equivalent to systemic TZD treatment. In addition to improved adipokine, inflammatory, and lipid profiles, PPARgamma activation in mature adipocytes normalizes serum insulin without increased adipogenesis. Co-culture studies indicated that PPARgamma-activated adipocytes broadly suppress induction of inflammatory cytokines and C-X-C family chemokines in macrophages. Collectively, these data describe an "adipocentric" model in which adipose activation of PPARgamma is sufficient for complete insulin sensitization and suggest a specific application for fat selective PPARgamma modulators in diabetic therapy.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pioglitazone	Peroxisome proliferator-activated receptor gamma	Protein	Humans	Yes	Agonist	Details