Hypothalamic IRX3: A New Player in the Development of Obesity

Trends Endocrinol Metab. 2020 May;31(5):368-377. doi: 10.1016/j.tem.2020.01.002. Epub 2020 Feb 5.


Genome-wide association studies (GWASs) have identified SNPs of the fat mass and obesity (FTO) gene as the most important risk alleles for obesity. However, how the presence of risk alleles affect phenotype is still a matter of intense investigation. In 2014, a study revealed that long-range enhancers from the intronic regions of the FTO gene regulate iroquois-class homeobox protein (IRX)3 expression. IRX3 is expressed in hypothalamic pro-opiomelanocortin (POMC) neurons and changes in its expression levels affect body adiposity by modifying food intake and energy expenditure. These findings have placed IRX3 as a potential target for the treatment of obesity. Here, we review studies that evaluated the roles of IRX3 in development, neurogenesis, and body energy homeostasis.

Keywords: brown adipose tissue; diet; energy expenditure; food intake; hypothalamus; pro-opiomelanocortin neurons.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / metabolism*
  • Animals
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Hypothalamus / metabolism*
  • Obesity / genetics
  • Obesity / metabolism*
  • Pro-Opiomelanocortin / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Homeodomain Proteins
  • IRX3 protein, human
  • Transcription Factors
  • Pro-Opiomelanocortin
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human