Abstract
Although peroxisome proliferator-activated receptorgamma(PPARγ) 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-offunction animal models to delineate the receptor's insulin-sensitizing actions. Unexpectedly, we find that selective activation of PPARγ 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, PPARγ activation in mature adipocytes normalizes serum insulin without increased adipogenesis. Co-culture studies indicated that PPARγ-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 PPARγ is sufficient for complete insulin sensitization and suggest a specific application for fat selective PPARγ modulators in diabetic therapy.
Original language | English (US) |
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Pages (from-to) | 22504-22509 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 106 |
Issue number | 52 |
DOIs | |
State | Published - Dec 19 2009 |
Externally published | Yes |
Keywords
- Inflammation
- Insulin signaling
- Metabolic syndrome
- Nuclear hormone receptors
ASJC Scopus subject areas
- General