A Review of Single-Nucleotide Polymorphisms in Orexigenic Neuropeptides Targeting G Protein-Coupled Receptors

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Many physiological pathways are involved in appetite, food intake, and the maintenance of energy homeostasis. In particular, neuropeptides within the central nervous system have been demonstrated to be critical signaling molecules for modulating appetite. Both anorexigenic (appetite-decreasing) and orexigenic (appetite-stimulating) neuropeptides have been described. The biological effects of these neuropeptides can be observed following central administration in animal models. This review focuses on single nucleotide polymorphisms (SNPs) in six orexigenic neuropeptides: agouti-related protein (AGRP), galanin, melanin concentrating hormone (MCH), neuropeptide Y (NPY), orexin A, and orexin B. Following a brief summary of the neuropeptides and their orexigenic activities, reports associating SNPs within the orexigenic neuropeptides to energy homeostasis, food intake, obesity, and BMI in humans are reviewed. Additionally, the NIH tool Variation Viewer was utilized to identify missense SNPs within the mature, biologically active neuropeptide sequences. For SNPs found through Variation Viewer, a concise discussion on relevant pharmacological structure-activity relationship studies for select SNPs is included. This review is meant to update reported orexigenic neuropeptide SNPs and demonstrate the potential utility of genomic sequence databases for finding SNPs that may result in altered receptor signaling for neuropeptide pathways associated with appetite.

Original languageEnglish (US)
Pages (from-to)1235-1246
Number of pages12
JournalACS Chemical Neuroscience
Issue number6
StatePublished - Jun 20 2018

Bibliographical note

Funding Information:
M.D.E. and C.H.-L. wrote and edited the manuscript, prepared the figures, and approved the final manuscript submission. Funding This work was supported by NIH Grants R01DK108893 and R01DK097838. The Haskell−Luevano laboratory is a recipient of a 2017 Wallin Neuroscience Discovery Fund Award through the University of Minnesota. M.D.E. is a recipient of an NIH Postdoctoral Fellowship (F32DK108402). Notes The authors declare no competing financial interest.

Publisher Copyright:
© 2018 American Chemical Society.


  • GPCR
  • SNP
  • Single-nucleotide polymorphisms
  • agouti-related protein
  • galanin
  • hormone
  • melanocyte concentrating hormone
  • neuropeptide Y
  • orexin A
  • orexin B
  • peptide
  • pharmacogenomics
  • polypharmacology


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