The physiological function of the agouti-related peptide gene: The control of weight and metabolic rate

Tooru M. Mizuno, Hideo Makimura, Charles V. Mobbs

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

The central melanocortin system plays an important role in the regulation of energy homeostasis both in rodents and humans, and melanocortin receptors appear to be the core of this system. Alpha-melanocyte-stimulating hormone (α-MSH) inhibits feeding through melanocrtin 3 and 4 receptors (MC3-R and MC4-R) as an endogenous agonist. Although mutations in the agouti gene cause an overexpression of agouti peptide which antagonizes effects of α-MSH at MC4-R in the brain and causes obese phenotypes, there was no evidence for the presence of an endogenous antagonist for MC3-R and MC4-R until agouti related protein (AGRP) was identified. AGRP is expressed primarily in the hypothalamic arcuate nucleus and central administration of AGRP stimulates feeding and weight gain, and decreases metabolic rate. Although a complete deletion of the AGRP gene does not produce any significant metabolic phenotypes, reduction in AGRP expression by RNA interference is associated with increased metabolic rate along with reduced weight gain. The currently available data suggest that elevated AGRP mRNA along with reduced proopiomelanocortin (POMC) mRNA is associated with many types of obesity and agents antagonizing the effect of AGRP may be a potential therapeutic target in treating obesity and obesity-associated disorders in which endogenous hypothalamic AGRP is elevated.

Original languageEnglish
Pages (from-to)425-433
Number of pages9
JournalAnnals of Medicine
Volume35
Issue number6
DOIs
StatePublished - 2003

Keywords

  • Agouti
  • Feeding
  • Hypothalamus
  • Melanocortin
  • Metabolism
  • Neuropeptide Y
  • Obesity

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