The effects of the β3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression

Valur Emilsson, Roger J. Summers, Stephanie Hamilton, Yong Ling Liu, Michael A. Cawthorne

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The mitochondrial uncoupling protein UCP-1 uncouples respiration from ATP synthesis in brown adipose tissue (BAT) and thus energy is dissipated as heat. Recently two further isoforms have been identified which may play a similar role in other tissues. We have determined the effects of the rodent-selective β3-adrenoceptor (β3-AR) agonist BRL 35135, on β3-AR and UCP mRNA levels in tissues from lean and obese (fa/fa) Zucker rats. β3-AR mRNA levels were reduced in fa/fa white (WAT) and brown (BAT) adipose tissue relative to levels in lean littermates. BRL 35135 treatment increased expression levels of β3-AR mRNA in both genotypes. UCP-2 and UCP-3 mRNA levels in BAT, WAT and skeletal muscle were reduced by 2-3 fold in the fa/fa rats relative to the lean rats. We confirm that BRL 35135 increases BAT UCP-1 mRNA in lean rats, and find that BAT UCP-3 mRNA was reduced 3.2 fold, with no changes in UCP-2 expression. In WAT BRL 35135 increased UCP-2 and UCP-3 expression 2-3 fold in both lean and fa/fa rats. In lean rats, skeletal muscle UCP-3 mRNA was increased 2.3 fold by BRL 35135 whereas UCP-2 was reduced by 2.2 fold. BRL 35135 had no effects on UCP-2 and UCP-3 expression in skeletal muscle of the fa/fa rats. Our results demonstrate that mechanisms regulating UCP isoform synthesis in fa/fa rats are impaired and that WAT could be involved in the thermogenic response of BRL 35135.

Original languageEnglish
Pages (from-to)450-454
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume252
Issue number2
DOIs
Publication statusPublished - 18 Nov 1998

Cite this

Emilsson, Valur ; Summers, Roger J. ; Hamilton, Stephanie ; Liu, Yong Ling ; Cawthorne, Michael A. / The effects of the β3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression. In: Biochemical and Biophysical Research Communications. 1998 ; Vol. 252, No. 2. pp. 450-454.
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abstract = "The mitochondrial uncoupling protein UCP-1 uncouples respiration from ATP synthesis in brown adipose tissue (BAT) and thus energy is dissipated as heat. Recently two further isoforms have been identified which may play a similar role in other tissues. We have determined the effects of the rodent-selective β3-adrenoceptor (β3-AR) agonist BRL 35135, on β3-AR and UCP mRNA levels in tissues from lean and obese (fa/fa) Zucker rats. β3-AR mRNA levels were reduced in fa/fa white (WAT) and brown (BAT) adipose tissue relative to levels in lean littermates. BRL 35135 treatment increased expression levels of β3-AR mRNA in both genotypes. UCP-2 and UCP-3 mRNA levels in BAT, WAT and skeletal muscle were reduced by 2-3 fold in the fa/fa rats relative to the lean rats. We confirm that BRL 35135 increases BAT UCP-1 mRNA in lean rats, and find that BAT UCP-3 mRNA was reduced 3.2 fold, with no changes in UCP-2 expression. In WAT BRL 35135 increased UCP-2 and UCP-3 expression 2-3 fold in both lean and fa/fa rats. In lean rats, skeletal muscle UCP-3 mRNA was increased 2.3 fold by BRL 35135 whereas UCP-2 was reduced by 2.2 fold. BRL 35135 had no effects on UCP-2 and UCP-3 expression in skeletal muscle of the fa/fa rats. Our results demonstrate that mechanisms regulating UCP isoform synthesis in fa/fa rats are impaired and that WAT could be involved in the thermogenic response of BRL 35135.",
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The effects of the β3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression. / Emilsson, Valur; Summers, Roger J.; Hamilton, Stephanie; Liu, Yong Ling; Cawthorne, Michael A.

In: Biochemical and Biophysical Research Communications, Vol. 252, No. 2, 18.11.1998, p. 450-454.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The effects of the β3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression

AU - Emilsson, Valur

AU - Summers, Roger J.

AU - Hamilton, Stephanie

AU - Liu, Yong Ling

AU - Cawthorne, Michael A.

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N2 - The mitochondrial uncoupling protein UCP-1 uncouples respiration from ATP synthesis in brown adipose tissue (BAT) and thus energy is dissipated as heat. Recently two further isoforms have been identified which may play a similar role in other tissues. We have determined the effects of the rodent-selective β3-adrenoceptor (β3-AR) agonist BRL 35135, on β3-AR and UCP mRNA levels in tissues from lean and obese (fa/fa) Zucker rats. β3-AR mRNA levels were reduced in fa/fa white (WAT) and brown (BAT) adipose tissue relative to levels in lean littermates. BRL 35135 treatment increased expression levels of β3-AR mRNA in both genotypes. UCP-2 and UCP-3 mRNA levels in BAT, WAT and skeletal muscle were reduced by 2-3 fold in the fa/fa rats relative to the lean rats. We confirm that BRL 35135 increases BAT UCP-1 mRNA in lean rats, and find that BAT UCP-3 mRNA was reduced 3.2 fold, with no changes in UCP-2 expression. In WAT BRL 35135 increased UCP-2 and UCP-3 expression 2-3 fold in both lean and fa/fa rats. In lean rats, skeletal muscle UCP-3 mRNA was increased 2.3 fold by BRL 35135 whereas UCP-2 was reduced by 2.2 fold. BRL 35135 had no effects on UCP-2 and UCP-3 expression in skeletal muscle of the fa/fa rats. Our results demonstrate that mechanisms regulating UCP isoform synthesis in fa/fa rats are impaired and that WAT could be involved in the thermogenic response of BRL 35135.

AB - The mitochondrial uncoupling protein UCP-1 uncouples respiration from ATP synthesis in brown adipose tissue (BAT) and thus energy is dissipated as heat. Recently two further isoforms have been identified which may play a similar role in other tissues. We have determined the effects of the rodent-selective β3-adrenoceptor (β3-AR) agonist BRL 35135, on β3-AR and UCP mRNA levels in tissues from lean and obese (fa/fa) Zucker rats. β3-AR mRNA levels were reduced in fa/fa white (WAT) and brown (BAT) adipose tissue relative to levels in lean littermates. BRL 35135 treatment increased expression levels of β3-AR mRNA in both genotypes. UCP-2 and UCP-3 mRNA levels in BAT, WAT and skeletal muscle were reduced by 2-3 fold in the fa/fa rats relative to the lean rats. We confirm that BRL 35135 increases BAT UCP-1 mRNA in lean rats, and find that BAT UCP-3 mRNA was reduced 3.2 fold, with no changes in UCP-2 expression. In WAT BRL 35135 increased UCP-2 and UCP-3 expression 2-3 fold in both lean and fa/fa rats. In lean rats, skeletal muscle UCP-3 mRNA was increased 2.3 fold by BRL 35135 whereas UCP-2 was reduced by 2.2 fold. BRL 35135 had no effects on UCP-2 and UCP-3 expression in skeletal muscle of the fa/fa rats. Our results demonstrate that mechanisms regulating UCP isoform synthesis in fa/fa rats are impaired and that WAT could be involved in the thermogenic response of BRL 35135.

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DO - 10.1006/bbrc.1998.9667

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