A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2

• Published in: Cell metabolism Vol. 5; no. 1; pp. 21 - 33
• Main Authors: Coppola, Anna, Liu, Zhong-Wu, Andrews, Zane B., Paradis, Eric, Roy, Marie-Claude, Friedman, Jeffrey M., Ricquier, Daniel, Richard, Denis, Horvath, Tamas L., Gao, Xiao-Bing, Diano, Sabrina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2007
• Subjects: 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; Iodothyronine Deiodinase Type II; Ion Channels - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; MOLNEURO; Neuroglia - metabolism; Neurons - metabolism; Neuropeptide Y - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Thermogenesis; Triiodothyronine - metabolism; Uncoupling Protein 2; MOLNEURO
• ISSN: 1550-4131; 1932-7420
• 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.