STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation

Anca D. Dobrian, Elena V. Galkina, Qian Ma, Margaret Hatcher, Sabai Myo Aye, Mathew J. Butcher, Kaiwen Ma, Bronson A. Haynes, Mark H. Kaplan, Jerry L. Nadler

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

of the seven members of the STAT family. STAT4 has a prominent role in mediating interleukin-12-induced T-helper cell type 1 lineage differentiation. T cells are key players in the maintenance of adipose tissue (AT) inflammation. The role of STAT4 in obesity and AT inflammation is unknown. We sought to determine the role of STAT4 in AT inflammation in obesity-induced insulin resistance. We studied STAT4-null mice on the C57Bl6/J background. We have found that STAT42/2C57Bl6/J mice develop high-fat diet-induced obesity (DIO) similar to wild-type controls, but that they have significantly improved insulin sensitivity and better glucose tolerance. Using flow cytometry and real-time PCR, we show that STAT42/2 mice with DIO produce significantly reduced numbers of inflammatory cytokines and chemokines in adipocytes, have reduced numbers of CD8+ cells, and display increased alternative (M2) macrophage polarization. CD8+ cells, but not CD4+ cells, from STAT42/2 mice displayed reduced in vitro migration. Also, we found that adipocyte inflammation is reduced and insulin signaling is improved in STAT42/2 mice with DIO. We have identified STAT4 as a key contributor to insulin resistance and AT inflammation in DIO. Targeting STAT4 activation could be a novel approach to reducing AT inflammation and insulin resistance in obesity.

Original languageEnglish (US)
Pages (from-to)4109-4121
Number of pages13
JournalDiabetes
Volume62
Issue number12
DOIs
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Dobrian, A. D., Galkina, E. V., Ma, Q., Hatcher, M., Aye, S. M., Butcher, M. J., Ma, K., Haynes, B. A., Kaplan, M. H., & Nadler, J. L. (2013). STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation. Diabetes, 62(12), 4109-4121. https://doi.org/10.2337/db12-1275