TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes
TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes
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TSH/TSHR 信号传导抑制脂肪细胞中脂肪酸合酶 (FASN) 的表达
DOI：
10.1002/jcp.24952
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发表时间：
2015-09-01
影响因子：
5.6
通讯作者：
Wang, Xiangdong
中科院分区：
文献类型：
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作者：
Chen, Jicui;Ren, Jianmin;Wang, Xiangdong
TSH/TSHR信号在脂肪细胞的脂质代谢调节中起作用。然而，确切的机制尚不清楚。在本研究中，我们确定的影响，促甲状腺激素对脂肪酸合成酶（fatty acid synthase，FSH）的表达，并探讨其潜在的机制。在体外，TSH在成熟脂肪细胞中降低mRNA和蛋白水平的FXR表达，并伴有蛋白激酶A（PKA）活化、cAMP反应元件结合蛋白（CREB）磷酸化以及细胞外信号调节激酶1/2（ERK 1/2）和c-Jun NH 2-末端激酶（JNK）活化。抑制PKA和ERK可部分消除TSH诱导的FASN下调，但抑制JNK则不然。与对照动物相比，饮食诱导肥胖的C57 BL/6小鼠内脏组织中的TSHR和FXR表达显著增加，而甲状腺TSHR表达正常。这些结果表明，TSHR的激活直接抑制成熟脂肪细胞中FGFAP的表达，可能是通过PKA和ERK介导的。在肥胖动物中，TSHR的这种功能似乎被抵消了。确切的机制需要进一步研究。J.细胞。230：2233-2239，2015。© 2015威利期刊公司.
TSH/TSHR signaling plays a role in the regulation of lipid metabolism in adipocytes. However, the precise mechanisms are not known. In the present study, we determined the effect of TSH on fatty acid synthase (FASN) expression, and explored the underlying mechanisms. In vitro, TSH reduced FASN expression in both mRNA and protein levels in mature adipocytes and was accompanied by protein kinase A (PKA) activation, cAMP‐response element binding protein (CREB) phosphorylation, as well as extracellular signal‐regulated kinase 1/2 (ERK1/2) and c‐Jun NH2‐terminal kinase (JNK) activation. TSH‐induced downregulation of FASN was partially abolished by inhibition of PKA and ERK, but not JNK. TSHR and FASN expression in visceral tissue was significantly increased in C57BL/6 mice with diet‐induced obesity compared with control animals, whereas thyroid TSHR expression was normal. These findings suggest that activation of TSHR directly inhibits FASN expression in mature adipocytes, possibly mediated by PKA and ERK. In obese animals, this function of TSHR seems to be counteracted. The precise mechanisms need further investigation. J. Cell. Physiol. 230: 2233–2239, 2015. © 2015 Wiley Periodicals, Inc.