Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo

Gagnon, AnneMarie; Antunes, Tayze T.; Ly, Tapraya; Pongsuwan, Patama; Gavin, Claire; Lochnan, Heather A.; Sorisky, Alexander

doi:10.1016/j.metabol.2009.08.018

« Previous Next »Metabolism - Clinical and Experimental
Volume 59, Issue 4 , Pages 547-553, April 2010

Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo

AnneMarie Gagnon
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5
Tayze T. Antunes
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5
Tapraya Ly
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5
Patama Pongsuwan
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6
Claire Gavin
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6
Heather A. Lochnan
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6
Alexander Sorisky
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6
- Corresponding author. Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6. Tel.: +1 613 737 8899x73320; fax: +1 613 737 8803.

Received 14 July 2009; accepted 25 August 2009. published online 21 October 2009.

Abstract

Thyroid-stimulating hormone (TSH) stimulates adipocyte lipolysis, but signal transduction pathways activated by TSH for this response have not been directly studied. Using differentiated 3T3-L1 adipocytes as well as primary human adipocytes, we characterized the lipolytic action of TSH with dose-response and time-course studies, and compared it with isoproterenol. Thyroid-stimulating hormone stimulated phosphorylation of perilipin and hormone-sensitive lipase (HSL). Inhibition of protein kinase A with H89 blocked TSH-stimulated lipolysis as well as phosphorylation of perilipin and HSL. Thyroid-stimulating hormone stimulated lipolysis in vivo, as indicated by an elevation in serum free fatty acid (FFA) levels after recombinant human TSH administration to thyroidectomized patients (42% increase, n = 19, P < .05). For patients with a body mass index less than 30 kg/m², the TSH-induced increase in serum FFA levels was 53% (n = 11, P < .05), whereas levels in patients with a body mass index of at least 30 kg/m² (n = 8) did not change after TSH treatment. In summary, TSH stimulates lipolysis and phosphorylation of perilipin and HSL in a protein kinase A–dependent manner in differentiated adipocytes in culture and raises serum FFA levels in vivo.