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Publication
GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose
inflammation 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
Submitted By Submitted Externally on 12/2/2019
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2019
Date Published 6/1/2019
Volume : Pages 116 : 11936 - 11945
PubMed Reference 31160440
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 ?-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.




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