Orexins mitigate obesity‐associated dysfunctions in mice
2024
Blais, Anne | Denis, Isabelle | Andriamihaja, Mireille | Gratio, Valérie | Champeil-Potokar, Gaelle | Laouirem, Samira | Chassac, Anais | Couvelard, Anne | Paradis, Valérie | Voisin, Thierry | Davila-Gay, Anne-Marie, A.-M. | Couvineau, Alain | Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) | This work was supported by the National Research Institute for Agriculture, Food and the Environment (INRAE); AgroParisTech; Paris-Saclay University; the National Institute of Health and Medical Research (Inserm); the Université Paris Cité; the French National Cancer Institute (INCA; PAIR Pancreas, grant number no. PAN18-045); and the National League Against Cancer (grant numbers R16020HH, GB/MA/CD/EP-12062).
International audience
Mostrar más [+] Menos [-]Inglés. 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.
Mostrar más [+] Menos [-]Palabras clave de AGROVOC
Información bibliográfica
Este registro bibliográfico ha sido proporcionado por Institut national de la recherche agronomique