title: Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists.
abstract: The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5'AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII's effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature.
authors: Brown Foundation Institute of Molecular Medicine, University of Texas Medical School at Houston, TX 77030, USA.
authors: Yuanzhong
authors: Y
authors: Xu
authors: Brown Foundation Institute of Molecular Medicine, University of Texas Medical School at Houston, TX 77030, USA.
authors: Eun Ran
authors: ER
authors: Kim
authors: Brown Foundation Institute of Molecular Medicine, University of Texas Medical School at Houston, TX 77030, USA; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors: Shengjie
authors: S
authors: Fan
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Yan
authors: Y
authors: Xia
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Yong
authors: Y
authors: Xu
authors: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors: Cheng
authors: C
authors: Huang
authors: Brown Foundation Institute of Molecular Medicine, University of Texas Medical School at Houston, TX 77030, USA; Programs in Neuroscience and Biochemistry, Graduate School of Biological Sciences, University of Texas Medical School at Houston, TX 77030, USA. Electronic address: qingchun.tong@uth.tmc.edu.
authors: Qingchun
authors: Q
authors: Tong
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010456:Peptides, Cyclic / Q000494:pharmacology*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000172:deficiency / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017483:Receptors, Vasopressin / Q000502:physiology; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C574273:MC4R protein, mouse; D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; D011943:Receptors, Adrenergic, beta; D017483:Receptors, Vasopressin; C079282:melanotan-II; D000521:alpha-MSH
keywords: Alpha-MSH; Body temperature; Energy expenditure; Feeding; MTII; Melanocortin