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Chang, Young Tae
복잡계 자기조립 연구단
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CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice

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Title
CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice
Author(s)
Wang, CH; Lundh, M; Fu, A; Kriszt, R; Huang, TL; Lynes, MD; Leiria, LO; Shamsi, F; Darcy, J; Greenwood, BP; Narain, NR; Tolstikov, V; Smith, KL; Emanuelli, B; Young-Tae Chang; Hagen, S; Danial, NN; Kiebish, MA; Tseng, YH
Publication Date
2020-08
Journal
SCIENCE TRANSLATIONAL MEDICINE, v.12, no.558, pp.eaaz8664
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
© 2020 The Authors, some rights reserved. Brown and brown-like beige/brite adipocytes dissipate energy and have been proposed as therapeutic targets to combat metabolic disorders. However, the therapeutic effects of cell-based therapy in humans remain unclear. Here, we created human brown-like (HUMBLE) cells by engineering human white preadipocytes using CRISPR-Cas9-SAM-gRNA to activate endogenous uncoupling protein 1 expression. Obese mice that received HUMBLE cell transplants showed a sustained improvement in glucose tolerance and insulin sensitivity, as well as increased energy expenditure. Mechanistically, increased arginine/nitric oxide (NO) metabolism in HUMBLE adipocytes promoted the production of NO that was carried by S-nitrosothiols and nitrite in red blood cells to activate endogenous brown fat and improved glucose homeostasis in recipient animals. Together, these data demonstrate the utility of using CRISPR-Cas9 technology to engineer human white adipocytes to display brown fat-like phenotypes and may open up cell-based therapeutic opportunities to combat obesity and diabetes
URI
https://pr.ibs.re.kr/handle/8788114/7694
DOI
10.1126/scitranslmed.aaz8664
ISSN
1946-6234
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > 1. Journal Papers (저널논문)
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