Central stimulatory effect of leptin on T3 production is mediated by brown adipose tissue type II deiodinase.
To assess whether intracerebroventricular leptin administration affects monodeiodinase type II (D2) activity in the tissues where it is expressed [cerebral cortex, hypothalamus, pituitary, and brown adipose tissue (BAT)], hepatic monodeiodinase type I (D1) activity was inhibited with propylthiouracil (PTU), and small doses of thyroxine (T4; 0.6 nmol. 100 g body wt(-1). day(-1)) were supplemented to compensate for the PTU-induced hypothyroidism. Two groups of rats were infused with leptin for 6 days, one of them being additionally treated with reverse triiodothyronine (rT3), an inhibitor of D2. Control rats were infused with vehicle and pair-fed the amount of food consumed by leptin-infused animals. Central leptin administration produced marked increases in D2 mRNA expression and activity in BAT, changes that were likely responsible for increased plasma T3 and decreased plasma T4 levels. Indeed, plasma T3 and T4 concentrations were unaltered by central leptin administration in the presence of rT3. The additional observation of a leptin-induced increased mRNA expression of BAT uncoupling protein-1 suggested that the effect on BAT D2 may be mediated by the sympathetic nervous system.
Cettour-Rose
Philippe
P
Division of Endocrinology and Diabetology, Department of Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva 14, Switzerland.
Burger
Albert G
AG
Meier
Christoph A
CA
Visser
Theo J
TJ
Rohner-Jeanrenaud
Françoise
F
D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002540:Cerebral Cortex / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007031:Hypothalamus / Q000201:enzymology; D007276:Injections, Intraventricular; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism*; D007473:Ion Channels; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D010902:Pituitary Gland / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000096:biosynthesis*; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II
D002352:Carrier Proteins; D007453:Iodide Peroxidase; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014284:Triiodothyronine; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C000604373:Ucp1 protein, rat