A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2.
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.
Coppola
Anna
A
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Liu
Zhong-Wu
ZW
Andrews
Zane B
ZB
Paradis
Eric
E
Roy
Marie-Claude
MC
Friedman
Jeffrey M
JM
Ricquier
Daniel
D
Richard
Denis
D
Horvath
Tamas L
TL
Gao
Xiao-Bing
XB
Diano
Sabrina
S
D054369:Agouti-Related Protein; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D004435:Eating; D005215:Fasting; D005247:Feeding Behavior; D049452:Green Fluorescent Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D022722:Thermogenesis; D014284:Triiodothyronine / Q000378:metabolism*; D000071246:Uncoupling Protein 2; D000097564:Iodothyronine Deiodinase Type II
D054369:Agouti-Related Protein; D049452:Green Fluorescent Proteins; D006153:Guanosine Diphosphate; D036341:Intercellular Signaling Peptides and Proteins; D007453:Iodide Peroxidase; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D014284:Triiodothyronine; D000071246:Uncoupling Protein 2; D000097564:Iodothyronine Deiodinase Type II; C515199:Agrp protein, mouse; C000604390:Ucp2 protein, mouse