Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation

A. C. Bianco, J. E. Silva

Research output: Contribution to journalArticle

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Abstract

We have examined the activity of three lipogenic enzymes [malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD), and acetyl coenzyme A (CoA) carboxylase], the activity of the mitochondrial FAD-dependent α-glycerolphosphate dehydrogenase (α-GPD), and the mitochondrial concentration of uncoupling protein (UCP) in brown adipose tissue (BAT) of euthyroid and hypothyroid rats, both at room temperature and in response to acute cold stress. These enzymes and UCP are important for the thermogenic response of BAT in adaptation to cold. The basal level of the lipogenic enzymes was normal or slightly elevated in hypothyroid rats maintained at 23°C, but the levels of α-GPD and UCP were markedly reduced. Forty-eight hours at 4°C resulted in an increase in the activity of G-6-PD, acetyl-CoA carboxylase, and α-GPD and in the concentration of UCP both in euthyroid and hypothyroid animals, but the levels reached were invariably less in hypothyroid animals, indicating that thyroid hormone is necessary for a full metabolic response of BAT under maximal demands. Of all variables measured, the most affected was UCP (only one-fifth of the response of euthyroid rats to cold) followed by α-GPD (~50% the euthyroid response). The administration of replacement doses of triiodothyronine (T3) to hypothyroid rats for 5-7 days did not normalize any of the BAT responses, whereas the replacement of thyroxine (T4) for only 2 days sufficed to normalize them all. This effect of T4 was abolished by preventing its conversion to T3 with iopanoic acid. The replacement of T3, though, normalized the level of all four enzymes in the liver and the serum concentration of T3. Dose-response relationship analysis of the UCP response to T3 indicated that the normalization of the response to cold requires saturation of the nuclear T3 receptors. We concluded, therefore, that the activation of the BAT 5'-deiodinase induced by cold exposure, is essential to provide the high levels of nuclear T3 required for the full expression of BAT thermogenic potential.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume253
Issue number3
StatePublished - Dec 1 1987

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Brown Adipose Tissue
Tissue
Rats
Enzymes
Acetyl-CoA Carboxylase
Proteins
Glucosephosphate Dehydrogenase
Animals
Iopanoic Acid
Glycerolphosphate Dehydrogenase
Thyroid Hormone Receptors
Iodide Peroxidase
Flavin-Adenine Dinucleotide
Triiodothyronine
Cytoplasmic and Nuclear Receptors
Thyroxine
Thyroid Hormones
Liver
Mitochondrial Uncoupling Proteins
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation. / Bianco, A. C.; Silva, J. E.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 253, No. 3, 01.12.1987.

Research output: Contribution to journalArticle

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abstract = "We have examined the activity of three lipogenic enzymes [malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD), and acetyl coenzyme A (CoA) carboxylase], the activity of the mitochondrial FAD-dependent α-glycerolphosphate dehydrogenase (α-GPD), and the mitochondrial concentration of uncoupling protein (UCP) in brown adipose tissue (BAT) of euthyroid and hypothyroid rats, both at room temperature and in response to acute cold stress. These enzymes and UCP are important for the thermogenic response of BAT in adaptation to cold. The basal level of the lipogenic enzymes was normal or slightly elevated in hypothyroid rats maintained at 23°C, but the levels of α-GPD and UCP were markedly reduced. Forty-eight hours at 4°C resulted in an increase in the activity of G-6-PD, acetyl-CoA carboxylase, and α-GPD and in the concentration of UCP both in euthyroid and hypothyroid animals, but the levels reached were invariably less in hypothyroid animals, indicating that thyroid hormone is necessary for a full metabolic response of BAT under maximal demands. Of all variables measured, the most affected was UCP (only one-fifth of the response of euthyroid rats to cold) followed by α-GPD (~50{\%} the euthyroid response). The administration of replacement doses of triiodothyronine (T3) to hypothyroid rats for 5-7 days did not normalize any of the BAT responses, whereas the replacement of thyroxine (T4) for only 2 days sufficed to normalize them all. This effect of T4 was abolished by preventing its conversion to T3 with iopanoic acid. The replacement of T3, though, normalized the level of all four enzymes in the liver and the serum concentration of T3. Dose-response relationship analysis of the UCP response to T3 indicated that the normalization of the response to cold requires saturation of the nuclear T3 receptors. We concluded, therefore, that the activation of the BAT 5'-deiodinase induced by cold exposure, is essential to provide the high levels of nuclear T3 required for the full expression of BAT thermogenic potential.",
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