Chen Jicui, Ren Jianmin, Jing Qingping, Lu Sumei, Zhang Yuchao, Liu Yuantao, Yu Cong, Gao Peng, Zong Chen, Li Xia, Wang Xiangdong
Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China.
J Cell Physiol. 2015 Sep;230(9):2233-9. doi: 10.1002/jcp.24952.
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.
促甲状腺激素/促甲状腺激素受体（TSH/TSHR）信号传导在脂肪细胞脂质代谢调节中发挥作用。然而，确切机制尚不清楚。在本研究中，我们确定了促甲状腺激素对脂肪酸合酶（FASN）表达的影响，并探讨了潜在机制。在体外，促甲状腺激素降低了成熟脂肪细胞中FASN的mRNA和蛋白质水平表达，并伴有蛋白激酶A（PKA）激活、环磷酸腺苷反应元件结合蛋白（CREB）磷酸化，以及细胞外信号调节激酶1/2（ERK1/2）和c-Jun氨基末端激酶（JNK）激活。抑制PKA和ERK可部分消除促甲状腺激素诱导的FASN下调，但抑制JNK则不能。与对照动物相比，饮食诱导肥胖的C57BL/6小鼠内脏组织中的TSHR和FASN表达显著增加，而甲状腺TSHR表达正常。这些发现表明，TSHR的激活直接抑制成熟脂肪细胞中FASN的表达，可能由PKA和ERK介导。在肥胖动物中，TSHR的这一功能似乎受到了抵消。确切机制需要进一步研究。
