Housing mice near vs. below thermoneutrality affects drug-induced weight loss but does not improve prediction of efficacy in humans.
Cell Rep
; 43(8): 114501, 2024 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-39067024
ABSTRACT
Evaluation of weight loss drugs is usually performed in diet-induced obese mice housed at â¼22°C. This is a cold stress that increases energy expenditure by â¼35% compared to thermoneutrality (â¼30°C), which may overestimate drug-induced weight loss. We investigated five anti-obesity mechanisms that have been in clinical development, comparing weight loss in mice housed at 22°C vs. 30°C. Glucagon-like peptide-1 (GLP-1), human fibroblast growth factor 21 (hFGF21), and melanocortin-4 receptor (MC4R) agonist induced similar weight losses. Peptide YY elicited greater vehicle-subtracted weight loss at 30°C (7.2% vs. 1.4%), whereas growth differentiation factor 15 (GDF15) was more effective at 22°C (13% vs. 6%). Independent of ambient temperature, GLP-1 and hFGF21 prevented the reduction in metabolic rate caused by weight loss. There was no simple rule for a better prediction of human drug efficacy based on ambient temperature, but since humans live at thermoneutrality, drug testing using mice should include experiments near thermoneutrality.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Dinamarca