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.
Ribeiro
M O
MO
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil 05508-900.
Lebrun
F L
FL
Christoffolete
M A
MA
Branco
M
M
Crescenzi
A
A
Carvalho
S D
SD
Negrão
N
N
Bianco
A C
AC
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