Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: Possible mode of function

Bo Ding, Björn Kull, Zhurong Liu, Salim Mottagui-Tabar, Håkan Thonberg, Harvest F. Gu, Anthony J. Brookes, Lars Grundemar, Christina Karlsson, Anders Hamsten, Peter Arner, Claes Göran Östenson, Suad Efendic, Magnus Monné, Gunnar Von Heijne, Per Eriksson, Claes Wahlestedt

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increased body mass index (BMI) in two separate Swedish populations of normal and overweight individuals. In vitro transcription and translation studies indicated the unlikelihood that this signal peptide variation affects the site of cleavage and targeting or uptake of NPY into the endoplasmic reticulum (ER). However, the mutant, and to a lesser extent the wild-type, signal peptide by themselves markedly potentiated NPY-induced food intake, as well as hypothalamic NPY receptor signaling. Our findings in humans strongly indicate that the NPY signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalRegulatory Peptides
Volume127
Issue number1-3
DOIs
StatePublished - Apr 15 2005
Externally publishedYes

    Fingerprint

Keywords

  • Association
  • Function
  • Neuropeptide Y
  • Obesity
  • Polymorphism

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Ding, B., Kull, B., Liu, Z., Mottagui-Tabar, S., Thonberg, H., Gu, H. F., Brookes, A. J., Grundemar, L., Karlsson, C., Hamsten, A., Arner, P., Östenson, C. G., Efendic, S., Monné, M., Von Heijne, G., Eriksson, P., & Wahlestedt, C. (2005). Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: Possible mode of function. Regulatory Peptides, 127(1-3), 45-53. https://doi.org/10.1016/j.regpep.2004.10.011