Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, 373, Bloco G, Cidade Universitária - Ilha do Fundão, Rio de Janeiro - RJ 21941-902, Brazil.
J Endocrinol. 2011 Oct;211(1):65-72. doi: 10.1530/JOE-11-0142. Epub 2011 Jul 13.
n-3 polyunsaturated fatty acids (n-3 PUFA) from fish oil (FO) exert important lipid-lowering effects, an effect also ascribed to thyroid hormones (TH) and TH receptor β1 (TRβ1)-specific agonists. n-3 PUFA effects are mediated by nuclear receptors, such as peroxisome proliferator-activated receptors (PPAR) and others. In this study, we investigated a role for TH signaling in n-3 PUFA effects. Euthyroid and hypothyroid adult rats (methimazole-treated for 5 weeks) received FO or soybean oil (control) by oral administration for 3 weeks. In euthyroid rats, FO treatment reduced serum triglycerides and cholesterol, diminished body fat, and increased protein content of the animals. In addition, FO-treated rats exhibited higher liver expression of TRβ1 and mitochondrial α-glycerophosphate dehydrogenase (mGPD), at protein and mRNA levels, but no alteration of glutathione S-transferase or type 1 deiodinase. In hypothyroid condition, FO induced reduction in serum cholesterol and increase in body protein content, but lost the ability to reduce triglycerides and body fat, and to induce TRβ1 and mGDP expression. FO did not change PPARα liver abundance regardless of thyroid state; however, hypothyroidism led to a marked increase in PPARα liver content but did not alter TRβ1 or TRα expression. The data suggest that part of the effect of n-3 PUFA from FO on lipid metabolism is dependent on TH signaling in specific steps and together with the marked upregulation of PPARα in liver of hypothyroid rats suggest important in vivo consequences of the cross-talking between those fatty acids and TH pathways in liver metabolism.
鱼油（FO）中的 n-3 多不饱和脂肪酸（n-3 PUFA）具有重要的降脂作用，这种作用也归因于甲状腺激素（TH）和 TH 受体 β1（TRβ1）特异性激动剂。n-3 PUFA 的作用是通过核受体介导的，如过氧化物酶体增殖物激活受体（PPAR）和其他受体。在这项研究中，我们研究了 TH 信号在 n-3 PUFA 作用中的作用。甲状腺功能正常和甲状腺功能减退的成年大鼠（用甲巯咪唑治疗 5 周）通过口服给予 FO 或大豆油（对照）3 周。在甲状腺功能正常的大鼠中，FO 处理降低了血清甘油三酯和胆固醇，减少了体脂肪，并增加了动物的蛋白质含量。此外，FO 处理的大鼠在蛋白质和 mRNA 水平上表现出更高的肝脏 TRβ1 和线粒体 α-甘油磷酸脱氢酶（mGPD）表达，但谷胱甘肽 S-转移酶或 1 型脱碘酶没有改变。在甲状腺功能减退的情况下，FO 诱导血清胆固醇降低和身体蛋白质含量增加，但失去了降低甘油三酯和体脂肪的能力，并诱导 TRβ1 和 mGDP 表达。无论甲状腺状态如何，FO 都不会改变 PPARα 肝脏丰度；然而，甲状腺功能减退导致 PPARα 肝脏含量显著增加，但不会改变 TRβ1 或 TRα 表达。数据表明，FO 中的部分 n-3 PUFA 对脂质代谢的影响部分依赖于特定步骤中的 TH 信号，并且与甲状腺功能减退大鼠肝脏中 PPARα 的明显上调一起表明，这些脂肪酸与 TH 途径在肝脏代谢中的相互作用具有重要的体内后果。
