A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2

Cell Metab. 2007 Jan;5(1):21-33. doi: 10.1016/j.cmet.2006.12.002.


The active thyroid hormone, triiodothyronine (T3), regulates mitochondrial uncoupling protein activity and related thermogenesis in peripheral tissues. Type 2 deiodinase (DII), an enzyme that catalyzes active thyroid hormone production, and mitochondrial uncoupling protein 2 (UCP2) are also present in the hypothalamic arcuate nucleus, where their interaction and physiological significance have not been explored. Here, we report that DII-producing glial cells are in direct apposition to neurons coexpressing neuropeptide Y (NPY), agouti-related protein (AgRP), and UCP2. Fasting increased DII activity and local thyroid hormone production in the arcuate nucleus in parallel with increased GDP-regulated UCP2-dependent mitochondrial uncoupling. Fasting-induced T3-mediated UCP2 activation resulted in mitochondrial proliferation in NPY/AgRP neurons, an event that was critical for increased excitability of these orexigenic neurons and consequent rebound feeding following food deprivation. These results reveal a physiological role for a thyroid-hormone-regulated mitochondrial uncoupling in hypothalamic neuronal networks.

Publication types

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

MeSH terms

  • Agouti-Related Protein
  • Animals
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Eating
  • Fasting*
  • Feeding Behavior*
  • Green Fluorescent Proteins
  • Guanosine Diphosphate / metabolism
  • Hypothalamus / cytology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Iodide Peroxidase / metabolism
  • Ion Channels / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism*
  • Neuroglia / metabolism
  • Neurons / metabolism*
  • Neuropeptide Y / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Thermogenesis*
  • Triiodothyronine / metabolism*
  • Uncoupling Protein 2


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • Neuropeptide Y
  • Proto-Oncogene Proteins c-fos
  • Ucp2 protein, mouse
  • Uncoupling Protein 2
  • Triiodothyronine
  • Guanosine Diphosphate
  • Green Fluorescent Proteins
  • iodothyronine deiodinase type II
  • Iodide Peroxidase