Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo.
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/m(2), 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/m(2) (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.
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6.
Annemarie
A
Gagnon
Tayze T
TT
Antunes
Tapraya
T
Ly
Patama
P
Pongsuwan
Claire
C
Gavin
Heather A
HA
Lochnan
Alexander
A
Sorisky
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D000328:Adult; D000818:Animals; D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006801:Humans; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008875:Middle Aged; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D002787:Sterol Esterase / Q000378:metabolism; D013965:Thyroidectomy; D013972:Thyrotropin / Q000494:pharmacology*
D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D000070778:Perilipin-1; D010750:Phosphoproteins; D013972:Thyrotropin; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase