PLX249001

GSE153337: STAT1 Dissociates Adipose Tissue Inflammation from Insulin Sensitivity in Obesity

  • Organsim mouse
  • Type RNASEQ
  • Target gene
  • Project ARCHS4

Purpose: To determine how STAT1 activity in white adipocytes affects insulin sensitivity.; Methods: Adipocyte specific (ADIPOQ-Cre) STAT1 fl/fl mice (STAT1 fKO) and littermate controls (STAT1 fl/fl) were placed on 60% HFD for 18 weeks, followed by metabolic phenoptying and tissue harvest for RNA-seq; Results: STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1 fKO) enhanced mitochondrial function and accelerated TCA cycle flux coupled with subcutaneous WAT hyperplasia. STAT1 fKO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFNg) activity enhanced insulin sensitivity in diet-induced obesity.; Conclusions: Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity. SOURCE: Sean Hartig (hartig@bcm.edu) - Hartig Laboratory Baylor College of Medicine

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