CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice
Research output: Contribution to journal › Journal article › peer-review
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.
Original language | English |
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Article number | eaaz8664 |
Journal | Science Translational Medicine |
Volume | 12 |
Issue number | 558 |
Number of pages | 15 |
ISSN | 1946-6234 |
DOIs | |
Publication status | Published - 2020 |
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704293/pdf/nihms-1639488.pdf
Accepted author manuscript
ID: 247540881