The T3 receptor β1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes

Raquel Martinez De Mena, Thomas (Tom) Scanlan, Maria Jesus Obregon

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Brown adipose tissue (BAT) thermogenesis increases when uncoupling protein-1 (UCP1) is activated adrenergically and requires T3. In humans, UCP1 activation in BAT seems involved in body weight maintenance. BAT type 2 deiodinase (D2) increases in response to adrenergic agents, producing the T3 required for UCP1 expression. T3 actions are mediated by thyroid hormone nuclear T3 receptors (TR), TRα and TRβ. Studies in mice suggest that TRβ is required for UCP1 induction, whereas TRα regulates body temperature and adrenergic sensitivity. In the present study, we compare the effects of T3 vs. specific TRβ1 and TRα1 agonists [GC-1 and CO23] on the adrenergic induction of UCP1 and D2 in cultured rat brown adipocytes. T3 and GC-1 produced similar increases on UCP1, whereas CO23 increased UCP1 only at high doses (50 nM). GC-1 at low doses (0.2-10 nM) was less potent than T3, increasing the adrenergic stimulation of D2 activity and mRNA. At higher doses, GC-1 further stimulated whereas T3 inhibited D2 activity but not D2 mRNA, suggesting posttranscriptional effects. CO23 had no effect on D2 activity but increased D2 mRNA. T3, GC-1, or CO23 by themselves did not increase UCP1 or D2 mRNA. High T3 doses shortened D2 half-life and increased D2 turnover via proteasome, whereas GC-1 did not change D2 stability. The α1- and α2-adrenergic D2 responses increased using high T 3 doses. In summary, T3 increases the adrenergic stimulation of UCP1 and D2 expression mostly via the TRβ1 isoform, and in brown adipocytes, D2 is protected from degradation by the action of T 3 on TRβ1.

Original languageEnglish (US)
Pages (from-to)5074-5083
Number of pages10
JournalEndocrinology
Volume151
Issue number10
DOIs
StatePublished - Oct 2010

Fingerprint

Brown Adipocytes
Thyroid Hormone Receptors
Iodide Peroxidase
Protein Isoforms
Adrenergic Agents
Brown Adipose Tissue
Messenger RNA
Uncoupling Protein 1
Thermogenesis
Proteasome Endopeptidase Complex
Cytoplasmic and Nuclear Receptors
Body Temperature
Thyroid Hormones
Half-Life
GC 1 compound

ASJC Scopus subject areas

  • Endocrinology

Cite this

The T3 receptor β1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes. / Martinez De Mena, Raquel; Scanlan, Thomas (Tom); Obregon, Maria Jesus.

In: Endocrinology, Vol. 151, No. 10, 10.2010, p. 5074-5083.

Research output: Contribution to journalArticle

Martinez De Mena, Raquel ; Scanlan, Thomas (Tom) ; Obregon, Maria Jesus. / The T3 receptor β1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes. In: Endocrinology. 2010 ; Vol. 151, No. 10. pp. 5074-5083.
@article{33144f7385064046a46c38730e570efc,
title = "The T3 receptor β1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes",
abstract = "Brown adipose tissue (BAT) thermogenesis increases when uncoupling protein-1 (UCP1) is activated adrenergically and requires T3. In humans, UCP1 activation in BAT seems involved in body weight maintenance. BAT type 2 deiodinase (D2) increases in response to adrenergic agents, producing the T3 required for UCP1 expression. T3 actions are mediated by thyroid hormone nuclear T3 receptors (TR), TRα and TRβ. Studies in mice suggest that TRβ is required for UCP1 induction, whereas TRα regulates body temperature and adrenergic sensitivity. In the present study, we compare the effects of T3 vs. specific TRβ1 and TRα1 agonists [GC-1 and CO23] on the adrenergic induction of UCP1 and D2 in cultured rat brown adipocytes. T3 and GC-1 produced similar increases on UCP1, whereas CO23 increased UCP1 only at high doses (50 nM). GC-1 at low doses (0.2-10 nM) was less potent than T3, increasing the adrenergic stimulation of D2 activity and mRNA. At higher doses, GC-1 further stimulated whereas T3 inhibited D2 activity but not D2 mRNA, suggesting posttranscriptional effects. CO23 had no effect on D2 activity but increased D2 mRNA. T3, GC-1, or CO23 by themselves did not increase UCP1 or D2 mRNA. High T3 doses shortened D2 half-life and increased D2 turnover via proteasome, whereas GC-1 did not change D2 stability. The α1- and α2-adrenergic D2 responses increased using high T 3 doses. In summary, T3 increases the adrenergic stimulation of UCP1 and D2 expression mostly via the TRβ1 isoform, and in brown adipocytes, D2 is protected from degradation by the action of T 3 on TRβ1.",
author = "{Martinez De Mena}, Raquel and Scanlan, {Thomas (Tom)} and Obregon, {Maria Jesus}",
year = "2010",
month = "10",
doi = "10.1210/en.2010-0533",
language = "English (US)",
volume = "151",
pages = "5074--5083",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "10",

}

TY - JOUR

T1 - The T3 receptor β1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes

AU - Martinez De Mena, Raquel

AU - Scanlan, Thomas (Tom)

AU - Obregon, Maria Jesus

PY - 2010/10

Y1 - 2010/10

N2 - Brown adipose tissue (BAT) thermogenesis increases when uncoupling protein-1 (UCP1) is activated adrenergically and requires T3. In humans, UCP1 activation in BAT seems involved in body weight maintenance. BAT type 2 deiodinase (D2) increases in response to adrenergic agents, producing the T3 required for UCP1 expression. T3 actions are mediated by thyroid hormone nuclear T3 receptors (TR), TRα and TRβ. Studies in mice suggest that TRβ is required for UCP1 induction, whereas TRα regulates body temperature and adrenergic sensitivity. In the present study, we compare the effects of T3 vs. specific TRβ1 and TRα1 agonists [GC-1 and CO23] on the adrenergic induction of UCP1 and D2 in cultured rat brown adipocytes. T3 and GC-1 produced similar increases on UCP1, whereas CO23 increased UCP1 only at high doses (50 nM). GC-1 at low doses (0.2-10 nM) was less potent than T3, increasing the adrenergic stimulation of D2 activity and mRNA. At higher doses, GC-1 further stimulated whereas T3 inhibited D2 activity but not D2 mRNA, suggesting posttranscriptional effects. CO23 had no effect on D2 activity but increased D2 mRNA. T3, GC-1, or CO23 by themselves did not increase UCP1 or D2 mRNA. High T3 doses shortened D2 half-life and increased D2 turnover via proteasome, whereas GC-1 did not change D2 stability. The α1- and α2-adrenergic D2 responses increased using high T 3 doses. In summary, T3 increases the adrenergic stimulation of UCP1 and D2 expression mostly via the TRβ1 isoform, and in brown adipocytes, D2 is protected from degradation by the action of T 3 on TRβ1.

AB - Brown adipose tissue (BAT) thermogenesis increases when uncoupling protein-1 (UCP1) is activated adrenergically and requires T3. In humans, UCP1 activation in BAT seems involved in body weight maintenance. BAT type 2 deiodinase (D2) increases in response to adrenergic agents, producing the T3 required for UCP1 expression. T3 actions are mediated by thyroid hormone nuclear T3 receptors (TR), TRα and TRβ. Studies in mice suggest that TRβ is required for UCP1 induction, whereas TRα regulates body temperature and adrenergic sensitivity. In the present study, we compare the effects of T3 vs. specific TRβ1 and TRα1 agonists [GC-1 and CO23] on the adrenergic induction of UCP1 and D2 in cultured rat brown adipocytes. T3 and GC-1 produced similar increases on UCP1, whereas CO23 increased UCP1 only at high doses (50 nM). GC-1 at low doses (0.2-10 nM) was less potent than T3, increasing the adrenergic stimulation of D2 activity and mRNA. At higher doses, GC-1 further stimulated whereas T3 inhibited D2 activity but not D2 mRNA, suggesting posttranscriptional effects. CO23 had no effect on D2 activity but increased D2 mRNA. T3, GC-1, or CO23 by themselves did not increase UCP1 or D2 mRNA. High T3 doses shortened D2 half-life and increased D2 turnover via proteasome, whereas GC-1 did not change D2 stability. The α1- and α2-adrenergic D2 responses increased using high T 3 doses. In summary, T3 increases the adrenergic stimulation of UCP1 and D2 expression mostly via the TRβ1 isoform, and in brown adipocytes, D2 is protected from degradation by the action of T 3 on TRβ1.

UR - http://www.scopus.com/inward/record.url?scp=77957279363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957279363&partnerID=8YFLogxK

U2 - 10.1210/en.2010-0533

DO - 10.1210/en.2010-0533

M3 - Article

VL - 151

SP - 5074

EP - 5083

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 10

ER -