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Proc. Natl. Acad. Sci. USA, First published June 3, 2019 | https://doi.org/10.1073/pnas.1822067116 GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

Injae Hwang^a, Kyuri Jo^b, Kyung Cheul Shin^a, Jong In Kim^a, Yul Ji^a, Yoon Jeong Park^a,c, Jeu Park^a, Yong Geun Jeon^a, Sojeong Ka^a, Sujin Suk^d, Hye Lim Noh^d, Sung Sik Choe^a, Assim A. Alfadda^e, Jason K. Kim^d, Sun Kim^b, and Jae Bum Kim^a,c,1

^a National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, 08826 Seoul, South Korea; ^b Department of Computer Science and Engineering, Seoul National University, 08826 Seoul, South Korea; ^c Department of Biophysics and Chemical Biology, Seoul National University, 08826 Seoul, South Korea;^d Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655; and ^e Obesity Research Center, College of Medicine, King Saud University, 11461 Riyadh, Saudi Arabia

¹To whom correspondence may be addressed.

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.

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

논문정보

형식Research article
게재일2019년 06월 (BRIC 등록일 2019-06-07)
연구진국내(교신)+국외 연구진
분야 생명과학 > 분자생물학

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