Moreno-Navarrete José María, Moreno María, Ortega Francisco, Xifra Gemma, Hong Shangyu, Asara John M, Serrano José C E, Jové Mariona, Pissios Pavlos, Blüher Matthias, Ricart Wifredo, Portero-Otin Manuel, Fernández-Real José Manuel
Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Girona, Spain.
Department of Medicine, Universitat de Girona, Girona, Spain.
FASEB J. 2017 Oct;31(10):4482-4491. doi: 10.1096/fj.201700161R. Epub 2017 Jun 23.
Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid-stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross-sectionally, AT TSH-β () mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT mRNA were also examined. The bidirectional relationship between cholesterol and were studied in isolated human adipocytes. mRNA was consistently detected in AT from euthyroid subjects, and positively associated with serum total- and LDL-cholesterol, and with AT-specific cholesterol metabolism-associated lipids [arachidonoyl cholesteryl ester, C8-dihydroceramide, -stearoyl-d-sphingosine, and GlcCer(18:0, 24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased mRNA in human AT, whereas excess cholesterol up-regulated mRNA in human adipocytes. In addition, recombinant human TSH α/β administration resulted in increased mRNA levels in human adipocytes. In mice, subcutaneous AT expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of as a paracrine factor that is modulated in parallel with cholesterol metabolism in human AT.-Moreno-Navarrete, J. M., Moreno, M., Ortega, F., Xifra, G., Hong, S., Asara, J. M., Serrano, J. C. E., Jové, M., Pissios, P., Blüher, M., Ricart, W., Portero-Otin, M., Fernández-Real, J. M. mRNA is linked to cholesterol metabolism in adipose tissue.
已知亚临床甲状腺功能减退与血清胆固醇升高有关。由于促甲状腺激素（TSH）对胆固醇生物合成具有诱导作用，我们旨在研究人脂肪组织（AT）中TSH mRNA与胆固醇代谢之间的关系。横断面研究中，在4个独立队列中评估了AT TSH-β（）mRNA与血清总胆固醇和低密度脂蛋白胆固醇以及AT脂质组学的关系。纵向研究中，还研究了他汀类药物以及饮食和运动对AT mRNA的影响。在分离的人脂肪细胞中研究了胆固醇与之间的双向关系。在甲状腺功能正常的受试者的AT中始终检测到mRNA，并且与血清总胆固醇和低密度脂蛋白胆固醇以及与AT特异性胆固醇代谢相关的脂质[花生四烯酰胆固醇酯、C8-二氢神经酰胺、-硬脂酰-d-鞘氨醇和GlcCer(18:0, 24:1)]呈正相关。用他汀类药物以及饮食和运动干预降低胆固醇会导致人AT中mRNA减少，而过量胆固醇会上调人脂肪细胞中的mRNA。此外，重组人TSHα/β给药导致人脂肪细胞中mRNA水平升高。在小鼠中，皮下AT表达水平与循环胆固醇水平直接相关。总之，目前的结果提供了新的证据，表明是一种旁分泌因子，在人AT中与胆固醇代谢平行调节。-莫雷诺-纳瓦雷特，J. M.，莫雷诺，M.，奥尔特加，F.，西弗拉，G.，洪，S.，阿萨拉，J. M.，塞拉诺，J. C. E.，乔韦，M.，皮西奥斯，P.，布卢赫，M.，里卡特，W.，波特罗-奥廷，M.，费尔南德斯-雷亚尔，J. M. mRNA与脂肪组织中的胆固醇代谢有关。
