title: Neuropeptide Y and agouti-related peptide mediate complementary functions of hyperphagia and reduced energy expenditure in leptin receptor deficiency.
abstract: Neuropeptide Y (NPY) and agouti-related peptide (AGRP) can produce hyperphagia, reduce energy expenditure, and promote triglyceride deposition in adipose depots. As these two neuropeptides are coexpressed within the hypothalamic arcuate nucleus and mediate a major portion of the obesity caused by leptin signaling deficiency, we sought to determine whether the two neuropeptides mediated identical or complementary actions. Because of separate neuropeptide receptors and signal transduction mechanisms, there is a possibility of distinct encoding systems for the feeding and energy expenditure aspects of leptin-regulated metabolism. We have genetically added NPY deficiency and/or AGRP deficiency to LEPR deficiency isolated to AGRP cells. Our results indicate that the obesity of LEPR deficiency in AGRP/NPY neurons can produce obesity with either AGRP or NPY alone with AGRP producing hyperphagia while NPY promotes reduced energy expenditure. The absence of both NPY and AGRP prevents the development of obesity attributable to isolated LEPR deficiency in AGRP/NPY neurons. Operant behavioral testing indicated that there were no alterations in the reward for a food pellet from the AGRP-specific LEPR deficiency.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 12401, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Luo
authors.forename: Genevieve
authors.initials: G
authors.lastname: Marcelin
authors.forename: Shun Mei
authors.initials: SM
authors.lastname: Liu
authors.forename: Gary
authors.initials: G
authors.lastname: Schwartz
authors.forename: Streamson
authors.initials: S
authors.lastname: Chua
mesh_terms: D050154:Adiposity / Q000235:genetics / Q000502:physiology; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006963:Hyperphagia / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*
chemical_list: D054369:Agouti-Related Protein; D009478:Neuropeptide Y; D054411:Receptors, Leptin; C515447:leptin receptor, mouse