PPARγ activation in adipocytes is sufficient for systemic insulin sensitization

Shigeki Sugii, Peter Olson, Dorothy D. Sears, Maziyar Saberi, Annette R. Atkins, Grant D. Barish, Suk Hyun Hong, Glenda L. Castro, Yun Qiang Yin, Michael C. Nelson, Gene Hsiao, David R. Greaves, Michael Downes, Ruth T. Yu, Jerrold M. Olefsky, Ronald M. Evans

Research output: Contribution to journalArticlepeer-review

223 Scopus citations


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 languageEnglish (US)
Pages (from-to)22504-22509
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - Dec 19 2009
Externally publishedYes


  • Inflammation
  • Insulin signaling
  • Metabolic syndrome
  • Nuclear hormone receptors

ASJC Scopus subject areas

  • General


Dive into the research topics of 'PPARγ activation in adipocytes is sufficient for systemic insulin sensitization'. Together they form a unique fingerprint.

Cite this