Orexins mitigate obesity-associated dysfunctions in mice.

Autor: Blais A; UMR-PNCA, Université Paris-Saclay, AgroParisTech, Palaiseau, France., Denis I; UMR-PNCA, Université Paris-Saclay, AgroParisTech, Palaiseau, France., Andriamihaja M; UMR-PNCA, Université Paris-Saclay, AgroParisTech, Palaiseau, France., Gratio V; INSERM UMR1149/Inflammation Research Center (CRI), Université Paris Cité, Paris, France., Champeil-Potokar G; UMR-PNCA, Université Paris-Saclay, AgroParisTech, Palaiseau, France., Laouirem S; INSERM UMR1149/Inflammation Research Center (CRI), Université Paris Cité, Paris, France., Chassac A; INSERM UMR1149/Inflammation Research Center (CRI), Université Paris Cité, Paris, France., Couvelard A; INSERM UMR1149/Inflammation Research Center (CRI), Université Paris Cité, Paris, France., Paradis V; INSERM UMR1149/Inflammation Research Center (CRI), Université Paris Cité, Paris, France., Voisin T; INSERM UMR1149/Inflammation Research Center (CRI), Université Paris Cité, Paris, France., Davila AM; UMR-PNCA, Université Paris-Saclay, AgroParisTech, Palaiseau, France., Couvineau A; INSERM UMR1149/Inflammation Research Center (CRI), Université Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2024 Oct; Vol. 32 (10), pp. 1897-1909.
DOI: 10.1002/oby.24120
Abstrakt: Objective: Obesity is a chronic disease that affects more than 400 million adults with severe comorbidities. The search for new treatments to reduce its negative consequences is necessary. Orexins are hypothalamic neuropeptides involved in various physiological processes related to obesity. The aim of this study was to investigate the consequences of chronic orexin-A treatment in mouse models.
Methods: Female wild-type C57BL/6 mice that were obesity-prone or obesity-resistant and mice that were deficient for orexin receptors were fed with a high-fat diet. Glucose tolerance, indirect calorimetry, expression of brain neuropeptides and receptors, microglial activation, and microbiota were determined to evaluate the role of orexins on metabolic flexibility.
Results: Orexin-A reduces weight gain in obesity-prone mice. This reduction is associated with a decrease in body fat, food intake, steatosis, and insulin resistance, as well as alterations of intestinal microbiota composition. A decreased expression of orexin receptors and neuropeptides involved in food intake was also observed in the hypothalamus.
Conclusions: Our data support the notion that orexin receptor signaling is involved in different aspects of energy metabolism and can mitigate several dysfunctions associated with obesity, suggesting that orexin receptors can represent new targets for obesity treatment.
(© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)
Databáze: MEDLINE
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