Pancreatic polypeptide controls energy homeostasis via npy6r signaling in the suprachiasmatic nucleus in mice

Ernie Yulyaningsih, Kim Loh, Shu Lin, Jackie Lau, Lei Zhang, Yanchuan Shi, Britt A. Berning, Ronaldo Enriquez, Frank Driessler, Laurence Macia, Ee Cheng Khor, Yue Qi, Paul Baldock, Amanda Sainsbury, Herbert Herzog*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)58-72
Number of pages15
JournalCell Metabolism
Volume19
Issue number1
DOIs
Publication statusPublished - 7 Jan 2014
Externally publishedYes

Keywords

  • VASOACTIVE-INTESTINAL-PEPTIDE
  • NEUROPEPTIDE-Y RECEPTOR
  • GROWTH-HORMONE
  • METABOLIC SYNDROME
  • CIRCADIAN-RHYTHMS
  • VPAC(2) RECEPTOR
  • HUMAN HOMOLOG
  • WEIGHT-GAIN
  • BODY-WEIGHT
  • FOOD-INTAKE

Cite this