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 Kaplan, Jerry L. Nadler

Research output: Contribution to journalArticle

15 Citations (Scopus)

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

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Insulin Resistance
Adipose Tissue
Obesity
Inflammation
Diet
Adipocytes
High Fat Diet
Cell Lineage
Interleukin-12
Chemokines
Real-Time Polymerase Chain Reaction
Flow Cytometry
Cell Count
Macrophages
Maintenance
Insulin
Cytokines
T-Lymphocytes
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Dobrian, A. D., Galkina, E. V., Ma, Q., Hatcher, M., Aye, S. M., Butcher, M. J., ... 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

STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation. / Dobrian, Anca D.; Galkina, Elena V.; Ma, Qian; Hatcher, Margaret; Aye, Sabai Myo; Butcher, Mathew J.; Ma, Kaiwen; Haynes, Bronson A.; Kaplan, Mark; Nadler, Jerry L.

In: Diabetes, Vol. 62, No. 12, 12.2013, p. 4109-4121.

Research output: Contribution to journalArticle

Dobrian, AD, Galkina, EV, Ma, Q, Hatcher, M, Aye, SM, Butcher, MJ, Ma, K, Haynes, BA, Kaplan, M & Nadler, JL 2013, 'STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation', Diabetes, vol. 62, no. 12, pp. 4109-4121. https://doi.org/10.2337/db12-1275
Dobrian AD, Galkina EV, Ma Q, Hatcher M, Aye SM, Butcher MJ et al. STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation. Diabetes. 2013 Dec;62(12):4109-4121. https://doi.org/10.2337/db12-1275
Dobrian, Anca D. ; Galkina, Elena V. ; Ma, Qian ; Hatcher, Margaret ; Aye, Sabai Myo ; Butcher, Mathew J. ; Ma, Kaiwen ; Haynes, Bronson A. ; Kaplan, Mark ; Nadler, Jerry L. / STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation. In: Diabetes. 2013 ; Vol. 62, No. 12. pp. 4109-4121.
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