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

Abstract:

: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.

authors

Hwang I,Jo K,Shin KC,Kim JI,Ji Y,Park YJ,Park J,Jeon YG,Ka S,Suk S,Noh HL,Choe SS,Alfadda AA,Kim JK,Kim S,Kim JB

doi

10.1073/pnas.1822067116

subject

Has Abstract

pub_date

2019-06-11 00:00:00

pages

11936-11945

issue

24

eissn

0027-8424

issn

1091-6490

pii

1822067116

journal_volume

116

pub_type

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