Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

Cell Metab. 2015 May 5;21(5):692-705. doi: 10.1016/j.cmet.2015.04.008.


Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / innervation*
  • Adipose Tissue, Brown / physiology*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / innervation
  • Adipose Tissue, White / physiology
  • Animals
  • Body Temperature Regulation*
  • Female
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Homeostasis
  • Ion Channels / genetics
  • Lipid Metabolism*
  • Male
  • Mice
  • Mitochondrial Proteins / genetics
  • Serotonergic Neurons / physiology*
  • Thermogenesis
  • Uncoupling Protein 1


  • Ion Channels
  • Mitochondrial Proteins
  • UCP1 protein, human
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Glucose