PPARgamma activation in adipocytes is sufficient for systemic insulin sensitization.

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.

authors

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

doi

10.1073/pnas.0912487106

subject

Has Abstract

pub_date

2009-12-29 00:00:00

pages

22504-9

issue

52

eissn

0027-8424

issn

1091-6490

pii

0912487106

journal_volume

106

pub_type

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