title: Chronic intracerebroventricular infusion of nociceptin/orphanin FQ produces body weight gain by affecting both feeding and energy metabolism in mice.
abstract: Nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for opioid receptor-like 1 (ORL1), is involved in various central functions, such as pain, psychological stress, locomotor activity, learning and memory, and feeding regulation. Of these functions, the role of N/OFQ in the regulation of feeding has been suggested by the fact that the central administration of N/OFQ leads to feeding behavior. However, the manner in which N/OFQ influences body weight control and subsequent obesity is unclear. To clarify the involvement of N/OFQ in the development of obesity, we evaluated the effects of intracerebroventricular infusion of N/OFQ on food intake and body weight in C57BL/6J mice that were fed a regular chow diet or moderately high-fat (MHF) diet (32.6% kcal fat). N/OFQ significantly increased food intake and body weight both in the regular diet- and MHF diet-fed mice, and these changes were more apparent in the MHF diet-fed mice. When we performed a pair-feeding study in N/OFQ intracerebroventricularly infused mice, N/OFQ did not cause body weight gain but increased white adipose tissue weight and plasma leptin, insulin, and cholesterol levels. N/OFQ reduced rectal temperature in pair-fed mice, in keeping with decreased UCP1 mRNA expression in brown adipose tissue. These results suggest that N/OFQ contributes to the development of obesity not only by inducing hyperphagia but also by decreasing energy expenditure.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co Ltd, Tsukuba, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsushita
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mashiko
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kanno
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ohta
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D006963:Hyperphagia / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D014665:Vasodilator Agents; D000097629:Nociceptin