title: Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance.
abstract: Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb(Nts) neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection of LepRb(Nts) neurons with local orexin (OX) neurons and the ventral tegmental area (VTA), Nts-LepRbKO mice exhibit altered regulation of OX neurons and the mesolimbic DA system. Thus, LHA LepRb(Nts) neurons mediate physiologic leptin action on OX neurons and the mesolimbic DA system, and contribute importantly to the control of energy balance.
authors: Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. ggehrke@med.umich.edu
authors: Gina M
authors: GM
authors: Leinninger
authors: Darren M
authors: DM
authors: Opland
authors: Young-Hwan
authors: YH
authors: Jo
authors: Miro
authors: M
authors: Faouzi
authors: Lyndsay
authors: L
authors: Christensen
authors: Laura A
authors: LA
authors: Cappellucci
authors: Christopher J
authors: CJ
authors: Rhodes
authors: Margaret E
authors: ME
authors: Gnegy
authors: Jill B
authors: JB
authors: Becker
authors: Emmanuel N
authors: EN
authors: Pothos
authors: Audrey F
authors: AF
authors: Seasholtz
authors: Robert C
authors: RC
authors: Thompson
authors: Martin G
authors: MG
authors: Myers
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D004734:Energy Metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008867:Microtomy; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D000068797:Orexins; D054411:Receptors, Leptin / Q000172:deficiency* / Q000235:genetics; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009479:Neuropeptides; D000068797:Orexins; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D009496:Neurotensin; D004298:Dopamine