title: Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding.
abstract: The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.
authors: Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Gina M
authors: GM
authors: Leinninger
authors: Young-Hwan
authors: YH
authors: Jo
authors: Rebecca L
authors: RL
authors: Leshan
authors: Gwendolyn W
authors: GW
authors: Louis
authors: Hongyan
authors: H
authors: Yang
authors: Jason G
authors: JG
authors: Barrera
authors: Hilary
authors: H
authors: Wilson
authors: Darren M
authors: DM
authors: Opland
authors: Miro A
authors: MA
authors: Faouzi
authors: Yusong
authors: Y
authors: Gong
authors: Justin C
authors: JC
authors: Jones
authors: Christopher J
authors: CJ
authors: Rhodes
authors: Streamson
authors: S
authors: Chua
authors: Sabrina
authors: S
authors: Diano
authors: Tamas L
authors: TL
authors: Horvath
authors: Randy J
authors: RJ
authors: Seeley
authors: Jill B
authors: JB
authors: Becker
authors: Heike
authors: H
authors: Münzberg
authors: Martin G
authors: MG
authors: Myers
mesh_terms: D000818:Animals; D001835:Body Weight; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D055879:Gene Knock-In Techniques; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000166:cytology
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D004298:Dopamine