5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver

Nat Neurosci. 2010 Dec;13(12):1457-9. doi: 10.1038/nn.2664. Epub 2010 Oct 31.

Abstract

Mice lacking 5-HT 2C receptors (5-HT(2C)Rs) displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT(2C)Rs only in pro-opiomelanocortin (POMC) neurons. 5-HT(2C)R deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT(2C)R agonist); these effects were restored when 5-HT(2C)Rs were re-expressed in POMC neurons. Our findings indicate that 5-HT(2C)Rs expressed by POMC neurons are physiologically relevant regulators of insulin sensitivity and glucose homeostasis in the liver.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Stem / metabolism
  • Gene Expression Regulation*
  • Glucose / metabolism
  • Homeostasis / physiology
  • Hypothalamus / metabolism
  • Insulin Resistance / physiology*
  • Liver / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neurons / metabolism*
  • Neurons / physiology
  • Pro-Opiomelanocortin / biosynthesis*
  • Pro-Opiomelanocortin / physiology
  • Receptor, Serotonin, 5-HT2C / biosynthesis*
  • Receptor, Serotonin, 5-HT2C / genetics
  • Receptor, Serotonin, 5-HT2C / physiology

Substances

  • Receptor, Serotonin, 5-HT2C
  • Pro-Opiomelanocortin
  • Glucose

Grant support