The hypothalamic arcuate nucleus and the control of peripheral substrates

Best Pract Res Clin Endocrinol Metab. 2014 Oct;28(5):725-37. doi: 10.1016/j.beem.2014.03.003. Epub 2014 Apr 4.


The arcuate nucleus (ARC) of the hypothalamus is particularly regarded as a critical platform that integrates circulating signals of hunger and satiety reflecting energy stores and nutrient availability. Among ARC neurons, pro-opiomelanocortin (POMC) and agouti-related protein and neuropeptide Y (NPY/AgRP neurons) are considered as two opposing branches of the melanocortin signaling pathway. Integration of circulating signals of hunger and satiety results in the release of the melanocortin receptor ligand α-melanocyte-stimulating hormone (αMSH) by the POMC neurons system and decreases feeding and increases energy expenditure. The orexigenic/anabolic action of NPY/AgRP neurons is believed to rely essentially on their inhibitory input onto POMC neurons and second-orders targets. Recent updates in the field have casted a new light on the role of the ARC neurons in the coordinated regulation of peripheral organs involved in the control of nutrient storage, transformation and substrate utilization independent of food intake.

Keywords: agouti-related peptide; autonomic nervous system; diabetes; hypothalamus; neuropeptide Y; nutrient partitioning; obesity; substrate utilization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agouti-Related Protein / metabolism
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Eating / physiology*
  • Energy Metabolism / physiology*
  • Homeostasis / physiology
  • Humans
  • Neurons / metabolism*
  • Neuropeptide Y / metabolism
  • Pro-Opiomelanocortin / metabolism
  • alpha-MSH / metabolism


  • Agouti-Related Protein
  • Neuropeptide Y
  • alpha-MSH
  • Pro-Opiomelanocortin