Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Department of Metabolic Diseases, Medical University of Białystok, Białystok, Poland.
Thyroid. 2022 Feb;32(2):206-214. doi: 10.1089/thy.2021.0351. Epub 2021 Nov 17.
Thyroid hormone (TH) regulates metabolic pathways which may interfere with insulin action. There is limited knowledge on adipose tissue (AT) and skeletal muscle (SM) expression of genes associated with TH action in relation to insulin sensitivity. The aim of this study was to analyze AT and SM expression of the genes associated with TH action in subjects with different degree of insulin sensitivity and the regulation of these genes by insulin and free fatty acids (FFA). The study group comprised 72 euthyroid male subjects: 36 normal weight subjects and 36 overweight/obese subjects. Two-hour hyperinsulinemic-euglycemic clamp and tissue biopsies were performed. In the subgroup of 20 subjects, 9 normal weight subjects and 11 overweight/obese subjects, clamp was prolonged to 6 hours and another clamp with Intralipid/heparin infusion was performed after 1 week. Tissue biopsies were performed before and after each clamp. Overweight/obese subjects had higher AT , , and , lower AT and , higher SM , and lower SM , , , and expression. In AT, and increased, whereas and decreased after the clamp only in normal weight individuals. decreased in both groups. In SM, decreased, whereas and increased after the clamp only in normal weight individuals. Tissue and decreased in both groups. Intralipid/heparin abolished these effects. Alterations in AT and SM expression of TH-related gene indicate a decreased tissue TH action in obesity. Inability to increase TH-related gene expression in obesity and during FFA oversupply may contribute to the aggravation of lipotoxicity.
甲状腺激素（TH）调节代谢途径，可能会干扰胰岛素的作用。关于与 TH 作用相关的基因在胰岛素敏感性方面在脂肪组织（AT）和骨骼肌（SM）中的表达，我们的了解有限。本研究的目的是分析不同胰岛素敏感性人群中与 TH 作用相关的基因在 AT 和 SM 中的表达，以及胰岛素和游离脂肪酸（FFA）对这些基因的调节。
研究组包括 72 名甲状腺功能正常的男性受试者：36 名正常体重受试者和 36 名超重/肥胖受试者。进行了 2 小时高胰岛素-正常血糖钳夹和组织活检。在 20 名受试者的亚组中，9 名正常体重受试者和 11 名超重/肥胖受试者，钳夹延长至 6 小时，1 周后进行另一次用 Intralipid/肝素输注的钳夹。在每次钳夹之前和之后进行组织活检。
超重/肥胖受试者的 AT 、 、 较高，而 AT 、 较低，SM 、 较高，SM 、 、 、 较低。在 AT 中， 、 增加，而 、 仅在正常体重个体中在钳夹后减少。在两组中均减少。在 SM 中， 减少，而 、 仅在正常体重个体中在钳夹后增加。组织 、 减少，两组均减少。Intralipid/肝素消除了这些影响。
TH 相关基因在 AT 和 SM 中的表达改变表明肥胖时组织 TH 作用降低。在肥胖和 FFA 供应过多时，无法增加 TH 相关基因的表达可能导致脂毒性加重。
