Thyroid-stimulating Hormone Inhibits Adipose Triglyceride Lipase in 3T3-L1 Adipocytes Through the PKA Pathway

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Jan 16

PMID 25590597

Citations 15

Authors

Dongqing Jiang

Shizhan Ma

Fei Jing

Chao Xu

Fang Yan

Aihong Wang

Jiajun Zhao

Affiliations

Soon will be listed here.

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.

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References

Zimmermann R, Haemmerle G, Wagner E, Strauss J, Kratky D, Zechner R . Decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone-sensitive lipase-deficient white adipose tissue. J Lipid Res. 2003; 44(11):2089-99. DOI: 10.1194/jlr.M300190-JLR200. View

Garg A, Vanderpump M . Subclinical thyroid disease. Br Med Bull. 2013; 107:101-16. DOI: 10.1093/bmb/ldt024. View

Marcus C, EHREN H, Bolme P, Arner P . Regulation of lipolysis during the neonatal period. Importance of thyrotropin. J Clin Invest. 1988; 82(5):1793-7. PMC: 442750. DOI: 10.1172/JCI113793. View

Janson A, Karlsson F, Bolme P, Bronnegard M, Marcus C . Effects of stimulatory and inhibitory thyrotropin receptor antibodies on lipolysis in infant adipocytes. J Clin Endocrinol Metab. 1995; 80(5):1712-6. DOI: 10.1210/jcem.80.5.7745024. View

Villena J, Roy S, Sarkadi-Nagy E, Kim K, Sul H . Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem. 2004; 279(45):47066-75. DOI: 10.1074/jbc.M403855200. View

Jenkins C, Mancuso D, Yan W, Sims H, Gibson B, Gross R . Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem. 2004; 279(47):48968-75. DOI: 10.1074/jbc.M407841200. View

Zimmermann R, Strauss J, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M . Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 2004; 306(5700):1383-6. DOI: 10.1126/science.1100747. View

Langin D, Dicker A, Tavernier G, Hoffstedt J, Mairal A, Ryden M . Adipocyte lipases and defect of lipolysis in human obesity. Diabetes. 2005; 54(11):3190-7. DOI: 10.2337/diabetes.54.11.3190. View

Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J . Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science. 2006; 312(5774):734-7. DOI: 10.1126/science.1123965. View

10.

Bartz R, Zehmer J, Zhu M, Chen Y, Serrero G, Zhao Y . Dynamic activity of lipid droplets: protein phosphorylation and GTP-mediated protein translocation. J Proteome Res. 2007; 6(8):3256-65. DOI: 10.1021/pr070158j. View

11.

Schmittgen T, Livak K . Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3(6):1101-8. DOI: 10.1038/nprot.2008.73. View

12.

Zechner R, Kienesberger P, Haemmerle G, Zimmermann R, Lass A . Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res. 2008; 50(1):3-21. DOI: 10.1194/jlr.R800031-JLR200. View

13.

Huijsman E, van de Par C, Economou C, van der Poel C, Lynch G, Schoiswohl G . Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice. Am J Physiol Endocrinol Metab. 2009; 297(2):E505-13. DOI: 10.1152/ajpendo.00190.2009. View

14.

Elgadi A, Zemack H, Marcus C, Norgren S . Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH-induced lipolysis. Biochem Biophys Res Commun. 2010; 393(3):526-30. DOI: 10.1016/j.bbrc.2010.02.042. View

15.

Gagnon A, Antunes T, Ly T, Pongsuwan P, Gavin C, Lochnan H . Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo. Metabolism. 2009; 59(4):547-53. DOI: 10.1016/j.metabol.2009.08.018. View

16.

Lu S, Guan Q, Liu Y, Wang H, Xu W, Li X . Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity. Lipids Health Dis. 2012; 11:17. PMC: 3285521. DOI: 10.1186/1476-511X-11-17. View

17.

Martinez-Gonzalez C, Wang H, Micklem B, Bolam J, Mena-Segovia J . Subpopulations of cholinergic, GABAergic and glutamatergic neurons in the pedunculopontine nucleus contain calcium-binding proteins and are heterogeneously distributed. Eur J Neurosci. 2012; 35(5):723-34. DOI: 10.1111/j.1460-9568.2012.08002.x. View

18.

Wanjia X, Chenggang W, Aihong W, Xiaomei Y, Jiajun Z, Chunxiao Y . A high normal TSH level is associated with an atherogenic lipid profile in euthyroid non-smokers with newly diagnosed asymptomatic coronary heart disease. Lipids Health Dis. 2012; 11:44. PMC: 3331821. DOI: 10.1186/1476-511X-11-44. View

19.

Mason R, Meex R, Lee-Young R, Canny B, Watt M . Phosphorylation of adipose triglyceride lipase Ser(404) is not related to 5'-AMPK activation during moderate-intensity exercise in humans. Am J Physiol Endocrinol Metab. 2012; 303(4):E534-41. DOI: 10.1152/ajpendo.00082.2012. View

20.

Pagnon J, Matzaris M, Stark R, Meex R, Macaulay S, Brown W . Identification and functional characterization of protein kinase A phosphorylation sites in the major lipolytic protein, adipose triglyceride lipase. Endocrinology. 2012; 153(9):4278-89. DOI: 10.1210/en.2012-1127. View