GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

Proc Natl Acad Sci U S A. 2019 Jun 11;116(24):11936-11945. doi: 10.1073/pnas.1822067116. Epub 2019 Jun 3.


Accumulating evidence suggests that subcutaneous and visceral adipose tissues are differentially associated with metabolic disorders. In obesity, subcutaneous adipose tissue is beneficial for metabolic homeostasis because of repressed inflammation. However, the underlying mechanism remains unclear. Here, we demonstrate that γ-aminobutyric acid (GABA) sensitivity is crucial in determining fat depot-selective adipose tissue macrophage (ATM) infiltration in obesity. In diet-induced obesity, GABA reduced monocyte migration in subcutaneous inguinal adipose tissue (IAT), but not in visceral epididymal adipose tissue (EAT). Pharmacological modulation of the GABAB receptor affected the levels of ATM infiltration and adipose tissue inflammation in IAT, but not in EAT, and GABA administration ameliorated systemic insulin resistance and enhanced insulin-dependent glucose uptake in IAT, accompanied by lower inflammatory responses. Intriguingly, compared with adipose-derived stem cells (ADSCs) from EAT, IAT-ADSCs played key roles in mediating GABA responses that repressed ATM infiltration in high-fat diet-fed mice. These data suggest that selective GABA responses in IAT contribute to fat depot-selective suppression of inflammatory responses and protection from insulin resistance in obesity.

Keywords: adipose tissue macrophage (ATM); adipose-derived stem cell (ADSC); epididymal adipose tissue (EAT); gamma (γ)-aminobutyric acid (GABA); inguinal adipose tissue (IAT).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Adiposity / genetics
  • Animals
  • Diet, High-Fat / adverse effects
  • Female
  • Humans
  • Inflammation / metabolism*
  • Insulin / metabolism
  • Intra-Abdominal Fat / metabolism
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Obesity / metabolism*
  • Stem Cells / metabolism*
  • Subcutaneous Tissue / metabolism*
  • gamma-Aminobutyric Acid / metabolism*


  • Insulin
  • gamma-Aminobutyric Acid