TY - JOUR
T1 - A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2
AU - Coppola, Anna
AU - Liu, Zhong-Wu
AU - Andrews, Zane Bruce
AU - Paradis, Eric
AU - Roy, Marie-Claude
AU - Friedman, Jeffrey M
AU - Ricquier, Daniel
AU - Richard, Denis
AU - Horvath, Tamas L
AU - Gao, Xiao-Bing
AU - Diano, Sabrina
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
UR - http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1783766&blobtype=pdf
U2 - 10.1016/j.cmet.2006.12.002
DO - 10.1016/j.cmet.2006.12.002
M3 - Article
SN - 1550-4131
VL - 5
SP - 21
EP - 33
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -