title: Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice.
abstract: Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r(-/-)) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. Npy6r(-/-) mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r(-/-), mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r(-/-), mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition.
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Ernie
authors.initials: E
authors.lastname: Yulyaningsih
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Loh
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Jackie
authors.initials: J
authors.lastname: Lau
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Yanchuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Britt A
authors.initials: BA
authors.lastname: Berning
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Enriquez
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Driessler
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Macia
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Ee Cheng
authors.initials: EC
authors.lastname: Khor
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Baldock
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia; School of Medical Sciences, Wallace Wurth Building, University of NSW, Botany Street, Sydney 2052, Australia; The Boden Institute of Obesity, Nutrition, Exercise, and Eating Disorders, Sydney Medical School, The University of Sydney, Medical Foundation Building, 92-94 Parramatta Road, Camperdown NSW 2006, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.affiliation: Neuroscience Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia; UNSW Medicine, ASGM Building, University of NSW, Botany Street, Sydney 2052, Australia. Electronic address: h.herzog@garvan.org.au.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
mesh_terms: D050154:Adiposity; D000818:Animals; D001835:Body Weight; D003345:Corticosterone / Q000378:metabolism; D004032:Diet; D004734:Energy Metabolism; D005247:Feeding Behavior; D005298:Fertility; D006706:Homeostasis; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000473:pathology; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000172:deficiency / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000473:pathology; D013851:Thinness / Q000097:blood / Q000473:pathology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D008024:Ligands; C102315:Npy6r protein, mouse; D011964:Receptors, Gastrointestinal Hormone; D017476:Receptors, Neuropeptide Y; D014660:Vasoactive Intestinal Peptide; D010191:Pancreatic Polypeptide; D007334:Insulin-Like Growth Factor I; D003345:Corticosterone