title: Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion.
abstract: Two known types of leptin-responsive neurons reside within the arcuate nucleus: the agouti gene-related peptide (AgRP)/neuropeptide Y (NPY) neuron and the proopiomelanocortin (POMC) neuron. By deleting the leptin receptor gene (Lepr) specifically in AgRP/NPY and/or POMC neurons of mice, we examined the several and combined contributions of these neurons to leptin action. Body weight and adiposity were increased by Lepr deletion from AgRP and POMC neurons individually, and simultaneous deletion in both neurons (A+P LEPR-KO mice) further increased these measures. Young (periweaning) A+P LEPR-KO mice exhibit hyperphagia and decreased energy expenditure, with increased weight gain, oxidative sparing of triglycerides, and increased fat accumulation. Interestingly, however, many of these abnormalities were attenuated in adult animals, and high doses of leptin partially suppress food intake in the A+P LEPR-KO mice. Although mildly hyperinsulinemic, the A+P LEPR-KO mice displayed normal glucose tolerance and fertility. Thus, AgRP/NPY and POMC neurons each play mandatory roles in aspects of leptin-regulated energy homeostasis, high leptin levels in adult mice mitigate the importance of leptin-responsiveness in these neurons for components of energy balance, suggesting the presence of other leptin-regulated pathways that partially compensate for the lack of leptin action on the POMC and AgRP/NPY neurons.
authors.affiliation: Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 12461, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: van de Wall
authors.forename: Rebecca
authors.initials: R
authors.lastname: Leshan
authors.forename: Allison W
authors.initials: AW
authors.lastname: Xu
authors.forename: Nina
authors.initials: N
authors.lastname: Balthasar
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppari
authors.forename: Shun Mei
authors.initials: SM
authors.lastname: Liu
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Jo
authors.forename: Robert G
authors.initials: RG
authors.lastname: MacKenzie
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Nae J
authors.initials: NJ
authors.lastname: Dun
authors.forename: Joel
authors.initials: J
authors.lastname: Elmquist
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
authors.forename: Carl
authors.initials: C
authors.lastname: de Luca
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.forename: Streamson C
authors.initials: SC
authors.lastname: Chua
mesh_terms: D054369:Agouti-Related Protein / Q000502:physiology*; D000818:Animals; D001823:Body Composition; D004435:Eating; D004734:Energy Metabolism; D005298:Fertility; D006946:Hyperinsulinism / Q000209:etiology; D006963:Hyperphagia; D007774:Lactation; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000502:physiology*; D054411:Receptors, Leptin / Q000502:physiology*
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D009478:Neuropeptide Y; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D011333:Pro-Opiomelanocortin