title: Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers.
abstract: Distinct brain peptidergic circuits govern peripheral energy homeostasis and related behavior. Here we report that mitochondrial uncoupling protein 2 (UCP2) is expressed discretely in neurons involved in homeostatic regulation. UCP2 protein was associated with the mitochondria of neurons, predominantly in axons and axon terminals. UCP2-producing neurons were found to be the targets of peripheral hormones, including leptin and gonadal steroids, and the presence of UCP2 protein in axonal processes predicted increased local brain mitochondrial uncoupling activity and heat production. In the hypothalamus, perikarya producing corticotropin-releasing factor, vasopressin, oxytocin, and neuropeptide Y also expressed UCP2. Furthermore, axon terminals containing UCP2 innervated diverse hypothalamic neuronal populations. These cells included those producing orexin, melanin-concentrating hormone, and luteinizing hormone-releasing hormone. When c-fos-expressing cells were analyzed in the basal brain after either fasting or cold exposure, it was found that all activated neurons received a robust UCP2 input on their perikarya and proximal dendrites. Thus, our data suggest the novel concept that heat produced by axonal UCP2 modulates neurotransmission in homeostatic centers, thereby coordinating the activity of those brain circuits that regulate daily energy balance and related autonomic and endocrine processes.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. tamas.horvath@yale.edu
authors.forename: T L
authors.initials: TL
authors.lastname: Horvath
authors.forename: C H
authors.initials: CH
authors.lastname: Warden
authors.forename: M
authors.initials: M
authors.lastname: Hajos
authors.forename: A
authors.initials: A
authors.lastname: Lombardi
authors.forename: F
authors.initials: F
authors.lastname: Goglia
authors.forename: S
authors.initials: S
authors.lastname: Diano
mesh_terms: D000818:Animals; D001831:Body Temperature; D001833:Body Temperature Regulation / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology*; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2