Thyroid-stimulating hormone inhibits adipose triglyceride lipase in 3T3-L1 adipocytes through the PKA pathway

PLoS One. 2015 Jan 15;10(1):e0116439. doi: 10.1371/journal.pone.0116439. eCollection 2015.

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.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dose-Response Relationship, Drug
  • Lipase / metabolism*
  • Mice
  • Mice, Knockout
  • Receptors, Thyrotropin / genetics
  • Receptors, Thyrotropin / metabolism
  • Signal Transduction / drug effects*
  • Thyrotropin / pharmacology*

Substances

  • Receptors, Thyrotropin
  • Thyrotropin
  • Cyclic AMP-Dependent Protein Kinases
  • Lipase

Grants and funding

This work was funded by The National Basic Research Program (2012CB524900; http://www.nsfc.gov.cn/); the National Natural Science Foundation (81230018, 81170794, 81370891, 81300644; http://www.nsfc.gov.cn/); the Chinese Society of Endocrinology (13050830468; http://www.china-endo.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.