title: TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes.
abstract: 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.
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Jicui
authors: J
authors: Chen
authors: Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China.
authors: Jianmin
authors: J
authors: Ren
authors: Department of Endocrinology, Zibo First Hospital, Zibo, Shandong, China.
authors: Qingping
authors: Q
authors: Jing
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Sumei
authors: S
authors: Lu
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Yuchao
authors: Y
authors: Zhang
authors: Department of Endocrinology, The Second Hospital of Shandong University, Jinan, China.
authors: Yuantao
authors: Y
authors: Liu
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Cong
authors: C
authors: Yu
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Peng
authors: P
authors: Gao
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Chen
authors: C
authors: Zong
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Xia
authors: X
authors: Li
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
authors: Xiangdong
authors: X
authors: Wang
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D009765:Obesity / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D054890:Fatty Acid Synthase, Type I; D017868:Cyclic AMP-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3