Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis in brown fat.
To study the thermal response of interscapular brown fat (IBF) to norepinephrine (NE), urethan-anesthetized rats (1.2 g/kg ip) maintained at 28-30 degrees C received a constant venous infusion of NE (0-2 x 10(4) pmol/min) over a period of 60 min. IBF temperatures (T(IBF)) were recorded with a small thermistor fixed under the IBF pad. Data were plotted against time and expressed as maximal variation (Deltat degrees C). Saline-injected rats showed a decrease in T(IBF) of approximately 0.6 degrees C. NE infusion increased T(IBF) by a maximum of approximately 3.0 degrees C at a dose of 10(4) pmol x min(-1) x 100 g body wt(-1). Surgically thyroidectomized (Tx) rats kept on 0.05% methimazole showed a flat response to NE. Treatment with thyroxine (T(4), 0.8 microg x 100 g(-1) x day(-1)) for 2-15 days normalized mitochondrial UCP1 (Western blotting) and IBF thermal response to NE, whereas iopanoic acid (5 mg x 100 g body wt(-1) x day(-1)) blocked the effects of T(4). Treatment with 3,5, 3'-triiodothyronine (T(3), 0.6 microg x 100 g body wt(-1) x day(-1)) for up to 15 days did not normalize UCP1 levels. However, these animals showed a normal IBF thermal response to NE. Cold exposure for 5 days or feeding a cafeteria diet for 20 days increased UCP1 levels by approximately 3.5-fold. Nevertheless, the IBF thermal response was only greater than that of controls when maximal doses of NE (2 x 10(4) pmol/min and higher) were used.


CONCLUSIONS
1) hypothyroidism is associated with a blunted IBF thermal response to NE; 2) two- to fourfold changes in mitochondrial UCP1 concentration are not necessarily translated into heat production during NE infusion.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil 05508-900.
M O
MO
Ribeiro
F L
FL
Lebrun
M A
MA
Christoffolete
M
M
Branco
A
A
Crescenzi
S D
SD
Carvalho
N
N
Negrão
A C
AC
Bianco
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D003080:Cold Temperature; D004032:Diet; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007473:Ion Channels; D007480:Iopanoic Acid / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D009638:Norepinephrine / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy; D013974:Thyroxine / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D014284:Triiodothyronine; D008713:Methimazole; D007480:Iopanoic Acid; D013974:Thyroxine; D009638:Norepinephrine