Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform--specific

In newborns and small mammals, cold-induced adaptive (or nonshivering) thermogenesis is produced primarily in brown adipose tissue (BAT). Heat production is stimulated by the sympathetic nervous system, but it has an absolute requirement for thyroid hormone. We used the thyroid hormone receptor-beta...

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Bibliographic Details
Published in:The Journal of clinical investigation 2001-07, Vol.108 (1), p.97-105
Main Authors: Ribeiro, M O, Carvalho, S D, Schultz, J J, Chiellini, G, Scanlan, T S, Bianco, A C, Brent, G A
Format: Article
Language:English
Subjects:
Acetates - pharmacology
Adaptation, Physiological - drug effects
Adipocytes - drug effects
Adipocytes - metabolism
Adipose Tissue, Brown - drug effects
Adipose Tissue, Brown - physiology
Animals
Carrier Proteins - biosynthesis
Carrier Proteins - genetics
Cold Temperature
Cyclic AMP - biosynthesis
Gene Expression Regulation - drug effects
Glycerolphosphate Dehydrogenase - biosynthesis
Glycerolphosphate Dehydrogenase - genetics
Heart Rate - drug effects
Humans
Hypothyroidism - complications
Hypothyroidism - drug therapy
Hypothyroidism - physiopathology
Ion Channels
Liver - drug effects
Liver - enzymology
Malate Dehydrogenase - biosynthesis
Malate Dehydrogenase - genetics
Male
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondrial Proteins
Norepinephrine - pharmacology
Phenols - pharmacology
Protein Isoforms - drug effects
Protein Isoforms - genetics
Protein Isoforms - physiology
Rats
Receptors, Thyroid Hormone - drug effects
Receptors, Thyroid Hormone - genetics
Receptors, Thyroid Hormone - physiology
Sympathetic Nervous System - physiology
Thermogenesis - drug effects
Thermogenesis - physiology
Thyroid Hormones - physiology
Triiodothyronine - pharmacology
Triiodothyronine - therapeutic use
Uncoupling Protein 1
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Summary:In newborns and small mammals, cold-induced adaptive (or nonshivering) thermogenesis is produced primarily in brown adipose tissue (BAT). Heat production is stimulated by the sympathetic nervous system, but it has an absolute requirement for thyroid hormone. We used the thyroid hormone receptor-beta--selective (TR-beta--selective) ligand, GC-1, to determine by a pharmacological approach whether adaptive thermogenesis was TR isoform--specific. Hypothyroid mice were treated for 10 days with varying doses of T3 or GC-1. The level of uncoupling protein 1 (UCP1), the key thermogenic protein in BAT, was restored by either T3 or GC-1 treatment. However, whereas interscapular BAT in T3-treated mice showed a 3.0 degrees C elevation upon infusion of norepinephrine, indicating normal thermogenesis, the temperature did not increase (
ISSN:0021-9738
DOI:10.1172/jci200112584