CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice

Research output: Contribution to journalJournal articlepeer-review

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CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice. / Wang, Chih-Hao; Lundh, Morten; Fu, Accalia; Kriszt, Rókus; 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.

In: Science Translational Medicine, Vol. 12, No. 558, eaaz8664, 2020.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Wang, C-H, 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, Chang, Y-T, Hagen, S, Danial, NN, Kiebish, MA & Tseng, Y-H 2020, 'CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice', Science Translational Medicine, vol. 12, no. 558, eaaz8664. https://doi.org/10.1126/scitranslmed.aaz8664

APA

Wang, C-H., Lundh, M., Fu, A., Kriszt, R., Huang, T. L., Lynes, M. D., Leiria, L. O., Shamsi, F., Darcy, J., Greenwood, B. P., Narain, N. R., Tolstikov, V., Smith, K. L., Emanuelli, B., Chang, Y-T., Hagen, S., Danial, N. N., Kiebish, M. A., & Tseng, Y-H. (2020). CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice. Science Translational Medicine, 12(558), [eaaz8664]. https://doi.org/10.1126/scitranslmed.aaz8664

Vancouver

Wang C-H, Lundh M, Fu A, Kriszt R, Huang TL, Lynes MD et al. CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice. Science Translational Medicine. 2020;12(558). eaaz8664. https://doi.org/10.1126/scitranslmed.aaz8664

Author

Wang, Chih-Hao ; Lundh, Morten ; Fu, Accalia ; Kriszt, Rókus ; 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. / CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice. In: Science Translational Medicine. 2020 ; Vol. 12, No. 558.

Bibtex

@article{482c6e9bd5f648ebb66e88800db73e46,
title = "CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice",
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.",
author = "Chih-Hao Wang and Morten Lundh and Accalia Fu and R{\'o}kus Kriszt and Huang, {Tian Lian} and Lynes, {Matthew D} and Leiria, {Luiz O} and Farnaz Shamsi and Justin Darcy and Greenwood, {Bennett P} and Narain, {Niven R} and Vladimir Tolstikov and Smith, {Kyle L} and Brice Emanuelli and Young-Tae Chang and Susan Hagen and Danial, {Nika N} and Kiebish, {Michael A} and Yu-Hua Tseng",
year = "2020",
doi = "10.1126/scitranslmed.aaz8664",
language = "English",
volume = "12",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "american association for the advancement of science",
number = "558",

}

RIS

TY - JOUR

T1 - CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice

AU - Wang, Chih-Hao

AU - Lundh, Morten

AU - Fu, Accalia

AU - Kriszt, Rókus

AU - Huang, Tian Lian

AU - Lynes, Matthew D

AU - Leiria, Luiz O

AU - Shamsi, Farnaz

AU - Darcy, Justin

AU - Greenwood, Bennett P

AU - Narain, Niven R

AU - Tolstikov, Vladimir

AU - Smith, Kyle L

AU - Emanuelli, Brice

AU - Chang, Young-Tae

AU - Hagen, Susan

AU - Danial, Nika N

AU - Kiebish, Michael A

AU - Tseng, Yu-Hua

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1126/scitranslmed.aaz8664

DO - 10.1126/scitranslmed.aaz8664

M3 - Journal article

C2 - 32848096

VL - 12

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 558

M1 - eaaz8664

ER -

ID: 247540881