CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice
SCIE
SCOPUS
- Title
- CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice
- Authors
- Wang, Chih-Hao; Lundh, Morten; Fu, Accalia; Kriszt, Rokus; Huang, Tian Lian; Lynes, Matthew D.; Leiria, Luiz O.; Shamsi, Farnaz; Darcy, Justin; Greenwood, Bennett P.; Narain, Niven R.; Tolstikov, Vladimir; Smith, Kyle L.; Emanuelli, Brice; Chang, Young-Tae; Hagen, Susan; Danial, Nika N.; Kiebish, Michael A.; Tseng, Yu-Hua
- Date Issued
- 2020-08
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Abstract
- 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://oasis.postech.ac.kr/handle/2014.oak/107850
- DOI
- 10.1126/scitranslmed.aaz8664
- ISSN
- 1946-6234
- Article Type
- Article
- Citation
- SCIENCE TRANSLATIONAL MEDICINE, vol. 12, no. 558, 2020-08
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- There are no files associated with this item.
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