title: Biphasic effect of melanocortin agonists on metabolic rate and body temperature.
abstract: The melanocortin system regulates metabolic homeostasis and inflammation. Melanocortin agonists have contradictorily been reported to both increase and decrease metabolic rate and body temperature. We find two distinct physiologic responses occurring at similar doses. Intraperitoneal administration of the nonselective melanocortin agonist MTII causes a melanocortin-4 receptor (Mc4r)-mediated hypermetabolism/hyperthermia. This is preceded by a profound, transient hypometabolism/hypothermia that is preserved in mice lacking any one of Mc1r, Mc3r, Mc4r, or Mc5r. Three other melanocortin agonists also caused hypothermia, which is actively achieved via seeking a cool environment, vasodilation, and inhibition of brown adipose tissue thermogenesis. These results suggest that the hypometabolic/hypothermic effect of MTII is not due to a failure of thermoregulation. The hypometabolism/hypothermia was prevented by dopamine antagonists, and MTII selectively activated arcuate nucleus dopaminergic neurons, suggesting that these neurons may contribute to the hypometabolism/hypothermia. We propose that the hypometabolism/hypothermia is a regulated response, potentially beneficial during extreme physiologic stress.
authors: Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Beth
authors: B
authors: Lute
authors: Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: William
authors: W
authors: Jou
authors: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Dalya M
authors: DM
authors: Lateef
authors: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Margalit
authors: M
authors: Goldgof
authors: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Cuiying
authors: C
authors: Xiao
authors: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Ramón A
authors: RA
authors: Piñol
authors: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Alexxai V
authors: AV
authors: Kravitz
authors: Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors: Nicole R
authors: NR
authors: Miller
authors: Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Yuning George
authors: YG
authors: Huang
authors: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors: Clemence
authors: C
authors: Girardet
authors: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors: Andrew A
authors: AA
authors: Butler
authors: Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Oksana
authors: O
authors: Gavrilova
authors: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: marc.reitman@nih.gov.
authors: Marc L
authors: ML
authors: Reitman
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044102:Receptor, Melanocortin, Type 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018492:Dopamine Antagonists; D044102:Receptor, Melanocortin, Type 1; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D044101:Receptors, Melanocortin; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; C086971:melanocortin 5 receptor; D000521:alpha-MSH