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大鼠白色脂肪组织中 D1 和 D2 脱碘酶的存在与调节。

Presence and regulation of D1 and D2 deiodinases in rat white adipose tissue.

机构信息

Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.

出版信息

Metabolism. 2011 Sep;60(9):1207-10. doi: 10.1016/j.metabol.2011.01.014. Epub 2011 Mar 11.

DOI:10.1016/j.metabol.2011.01.014
PMID:21397282
Abstract

Thyroid hormones regulate adipogenic differentiation, lipogenic and lipolytic metabolism, and mitochondrial activity in adipose tissue. Triiodothyronine (T3) levels in tissues are regulated by the deiodinase enzymes. The objective was to study the activity and messenger RNA (mRNA) expression of the 5' outer-ring deiodinases (type 1 [D1] and type 2 [D2] deiodinase) and thyroid hormone concentrations in rat white adipose tissue (WAT), where only D1 activity had been described. Control, thyroidectomized, and thyroid hormone-treated rats were used. Type 1 and type 2 deiodinase mRNAs were determined in WAT by quantitative real-time polymerase chain reaction using Taqman probes; D1 and D2 activities were determined using reverse T3 and thyroxine (T4) as substrates. Thyroxine and T3 were measured by radioimmunoassay in plasma, liver, and adipose tissue. Type 1 and type 2 deiodinase mRNAs are present in epididymal rat WAT with similar abundance, which is 7% of the D2 mRNA levels in brown adipose tissue and 1% of D1 in liver. The Michaelis-Menten constants in WAT are 40 nmol/L T4 for D2 and 0.35 μmol/L reverse T3 for D1. Both D1 and D2 are regulated in rat epididymal WAT by thyroidal status. Thyroxine and T3 concentrations in plasma, liver, and WAT decreased after thyroidectomy and recovered after treatment with T4 + T3. Both D1 and D2 mRNAs increased in WAT from thyroidectomy rats; and T4 + T3 treatment inhibited them, especially D2 mRNA. Type 1 deiodinase activity did not change with thyroidal status, whereas D2 activity was inhibited by T4 + T3. The presence of both deiodinases in WAT suggests important roles in regulating T3 bioavailability for adipose tissue function and regulation of lipid metabolism and thermogenesis.

摘要

甲状腺激素调节脂肪生成分化、脂肪生成和脂肪分解代谢以及脂肪组织中的线粒体活性。组织中的三碘甲状腺原氨酸 (T3) 水平受脱碘酶的调节。目的是研究大鼠白色脂肪组织 (WAT) 中 5'外环脱碘酶 (1 型 [D1] 和 2 型 [D2] 脱碘酶) 的活性和信使 RNA (mRNA) 表达以及甲状腺激素浓度,其中仅描述了 D1 活性。使用对照、甲状腺切除和甲状腺激素处理的大鼠进行研究。通过 Taqman 探针的定量实时聚合酶链反应测定 WAT 中的 1 型和 2 型脱碘酶 mRNAs;使用反 T3 和甲状腺素 (T4) 作为底物测定 D1 和 D2 活性。通过放射免疫测定法在血浆、肝脏和脂肪组织中测量甲状腺素和 T3。1 型和 2 型脱碘酶 mRNAs 存在于大鼠附睾 WAT 中,丰度相似,在棕色脂肪组织中为 D2 mRNA 水平的 7%,在肝脏中为 D1 的 1%。WAT 中的米氏常数分别为 D2 的 40nmol/L T4 和 D1 的 0.35μmol/L 反 T3。甲状腺状态调节大鼠附睾 WAT 中的 D1 和 D2。甲状腺切除后,血浆、肝脏和 WAT 中的甲状腺素和 T3 浓度降低,甲状腺素+T3 治疗后恢复。甲状腺切除大鼠的 WAT 中 D1 和 D2 mRNA 均增加;甲状腺素+T3 治疗抑制了它们,特别是 D2 mRNA。甲状腺状态不改变 1 型脱碘酶活性,而 T4+T3 抑制 D2 活性。WAT 中两种脱碘酶的存在表明其在调节脂肪组织功能和脂质代谢及产热的 T3 生物利用度方面发挥重要作用。

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