CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
26 08 2020
26 08 2020
Historique:
received:
16
10
2019
revised:
24
02
2020
accepted:
03
08
2020
entrez:
28
8
2020
pubmed:
28
8
2020
medline:
24
6
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 32848096
pii: 12/558/eaaz8664
doi: 10.1126/scitranslmed.aaz8664
pmc: PMC7704293
mid: NIHMS1639488
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK102898
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK078081
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007260
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK077097
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK111714
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK102320
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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