Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3.
Bombesin receptor subtype-3 (BRS-3) regulates energy homeostasis, with Brs3 knockout (Brs3(-/y)) mice being hypometabolic, hypothermic, and hyperphagic and developing obesity. We now report that the reduced body temperature is more readily detected if body temperature is analyzed as a function of physical activity level and light/dark phase. Physical activity level correlated best with body temperature 4 min later. The Brs3(-/y) metabolic phenotype is not due to intrinsically impaired brown adipose tissue function or in the communication of sympathetic signals from the brain to brown adipose tissue, since Brs3(-/y) mice have intact thermogenic responses to stress, acute cold exposure, and β3-adrenergic activation, and Brs3(-/y) mice prefer a cooler environment. Treatment with the BRS-3 agonist MK-5046 increased brown adipose tissue temperature and body temperature in wild-type but not Brs3(-/y) mice. Intrahypothalamic infusion of MK-5046 increased body temperature. These data indicate that the BRS-3 regulation of body temperature is via a central mechanism, upstream of sympathetic efferents. The reduced body temperature in Brs3(-/y) mice is due to altered regulation of energy homeostasis affecting higher center regulation of body temperature, rather than an intrinsic defect in brown adipose tissue.
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; and.
Dalya M
DM
Lateef
Gustavo
G
Abreu-Vieira
Cuiying
C
Xiao
Marc L
ML
Reitman
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D058639:Cold-Shock Response / Q000187:drug effects; D003433:Crosses, Genetic; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D057967:Infusions, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D018004:Receptors, Bombesin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D022722:Thermogenesis / Q000187:drug effects
C556243:1,1,1-trifluoro-2-(4-(1H-pyrazol-1-yl)phenyl)-3-(4-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-imidazol-2-yl)propan-2-ol; D058667:Adrenergic beta-3 Receptor Agonists; D004149:Dioxoles; D007093:Imidazoles; D009419:Nerve Tissue Proteins; D011720:Pyrazoles; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
CL316243; MK-5046; bombesin receptor subtype-3; brown adipose tissue; obesity; sympathetic nervous system; thermoregulation