title: Thyroid-stimulating hormone inhibits adipose triglyceride lipase in 3T3-L1 adipocytes through the PKA pathway.
abstract: Thyroid-stimulating hormone (TSH) has been shown to play an important role in the regulation of triglyceride (TG) metabolism in adipose tissue. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme controlling the hydrolysis of TG. Thus far, it is unclear whether TSH has a direct effect on the expression of ATGL. Because TSH function is mediated through the TSH receptor (TSHR), TSHR knockout mice (Tshr-/- mice) (supplemented with thyroxine) were used in this study to determine the effects of TSHR deletion on ATGL expression. These effects were verified in 3T3-L1 adipocytes and potential underlying mechanisms were explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was significantly increased compared with that in Tshr+/+ mice. ATGL expression was observed to increase with the differentiation process of 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1 adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by H89, which is a protein kinase A (PKA) inhibitor. These results indicate that TSH has an inhibitory effect on ATGL expression in mature adipocytes. The associated mechanism is related to PKA activation.
authors.affiliation: Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China; Department of Endocrinology and Metabolism, The Second Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China; Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan, Shandong, China.
authors.forename: Shizhan
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China; Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan, Shandong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Jing
authors.affiliation: Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China; Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan, Shandong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China; Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan, Shandong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China; Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan, Shandong, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008049:Lipase / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013972:Thyrotropin / Q000494:pharmacology*
chemical_list: D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D017868:Cyclic AMP-Dependent Protein Kinases; D008049:Lipase