title: Orexin neurons are indispensable for stress-induced thermogenesis in mice.
abstract: Orexin neurons contribute to cardiovascular, respiratory and analgesic components of the fight-or-flight response against stressors. Here, we examined whether the same is true for stress-induced hyperthermia. We used prepro-orexin knockout mice (ORX-KO) and orexin neuron-ablated mice (ORX-AB) in which the latter lack not only orexin, but also other putative neurotransmitter/modulators contained in the orexin neurons. In response to repetitive insertion of a temperature probe into their rectum (handling stress), ORX-KO mice showed a normal temperature change as compared to that of wild-type littermates (WT) while ORX-AB showed an attenuated response. Stress-induced expression of uncoupling protein-1, a key molecule in non-shivering thermogenesis in the brown adipose tissue (BAT), was also blunted in ORX-AB but not in ORX-KO. When the BAT was directly activated by a β3 adrenergic agonist, there was no difference in the resultant BAT temperature among the groups, indicating that BAT per se was normal in ORX-AB. In WT and ORX-KO, handling stress activated orexin neurons (as revealed by increased expression of c-Fos) and the resultant hyperthermia was largely blunted by pre-treatment with a β3 antagonist. This observation further supports the notion that attenuated stress-induced hyperthermia in ORX-AB mice was caused by a loss of orexin neurons and abnormal BAT regulation. This study pointed out, for the first time, the possible importance of co-existent neurotransmitter/modulators in the orexin neurons for stress-induced hyperthermia and the importance of integrity of the orexin neurons for full expression of multiple facets of the fight-or-flight response.
authors.affiliation: Department of Molecular and Integrative Physiology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jinko
authors.initials: J
authors.lastname: Sunanaga
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Taketsugu
authors.initials: T
authors.lastname: Mori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kanmura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kuwaki
mesh_terms: D055011:Ablation Techniques; D000222:Adaptation, Physiological / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000502:physiology; D023421:Models, Animal; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology*; D000071256:Uncoupling Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
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