title: Impact of Orexin-A Treatment on Food Intake, Energy Metabolism and Body Weight in Mice.
abstract: Orexin-A and -B are hypothalamic neuropeptides of 33 and 28-amino acids, which regulate many homeostatic systems including sleep/wakefulness states, energy balance, energy homeostasis, reward seeking and drug addiction. Orexin-A treatment was also shown to reduce tumor development in xenografted nude mice and is thus a potential treatment for carcinogenesis. The aim of this work was to explore in healthy mice the consequences on energy expenditure components of an orexin-A treatment at a dose previously shown to be efficient to reduce tumor development. Physiological approaches were used to evaluate the effect of orexin-A on food intake pattern, energy metabolism body weight and body adiposity. Modulation of the expression of brain neuropeptides and receptors including NPY, POMC, AgRP, cocaine- and amphetamine related transcript (CART), corticotropin-releasing hormone (CRH) and prepro-orexin (HCRT), and Y2 and Y5 neuropeptide Y, MC4 (melanocortin), OX1 and OX2 orexin receptors (Y2R, Y5R, MC4R, OX1R and OX2R, respectively) was also explored. Our results show that orexin-A treatment does not significantly affect the components of energy expenditure, and glucose metabolism but reduces intraperitoneal fat deposit, adiposity and the expression of several brain neuropeptide receptors suggesting that peripheral orexin-A was able to reach the central nervous system. These findings establish that orexin-A treatment which is known for its activity as an inducer of tumor cell death, do have minor parallel consequence on energy homeostasis control.
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Blais
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Drouin
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaumontet
authors.affiliation: INSERM U1149/ Inflammation Research Center (CRI), Paris-Diderot University, DHU UNITY, Faculté de Médecine Site Bichat, 16, rue H. Huchard, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Voisin
authors.affiliation: INSERM U1149/ Inflammation Research Center (CRI), Paris-Diderot University, DHU UNITY, Faculté de Médecine Site Bichat, 16, rue H. Huchard, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France.
authors.forename: Patrick Christian
authors.initials: PC
authors.lastname: Even
authors.affiliation: INSERM U1149/ Inflammation Research Center (CRI), Paris-Diderot University, DHU UNITY, Faculté de Médecine Site Bichat, 16, rue H. Huchard, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Couvineau
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D064446:Orexin Receptors / Q000378:metabolism; D000068797:Orexins / Q000494:pharmacology*
chemical_list: D064446:Orexin Receptors; D000068797:Orexins