Impaired metabolic effects of a thyroid hormone receptor beta-selective agonist in a mouse model of diet-induced obesity
Tipo
Artigo
Data de publicação
2010
Periódico
Thyroid
Citações (Scopus)
24
Autores
Castillo M.
Freitas B.C.G.
Rosene M.L.
Drigo R.A.
Grozovsky R.
MacIel R.M.B.
Patti M.E.
Ribeiro M.O.
Bianco A.C.
Freitas B.C.G.
Rosene M.L.
Drigo R.A.
Grozovsky R.
MacIel R.M.B.
Patti M.E.
Ribeiro M.O.
Bianco A.C.
Orientador
Título da Revista
ISSN da Revista
Título de Volume
Membros da banca
Programa
Resumo
Background: The use of selective agonists of the thyroid hormone receptor isoform β (TRβ) has been linked to metabolic improvement in animal models of diet-induced obesity, nonalcoholic liver disease, and genetic hypercholesterolemia. Methods: To identify potential target tissues of such compounds, we exposed primary murine brown adipocytes and skeletal myocytes for 24 hours to 50 nM GC-24, a highly selective TRβ agonist. GC-24 (17 ng/[g BW•day] for 36 days) was also tested in a mouse model of diet-induced obesity. Results: While the brown adipocytes responded to GC-24, with 17%-400% increases in the expression of 12 metabolically relevant genes, the myocytes remained largely unresponsive to GC-24 treatment. In control mice kept on chow diet, GC-24 treatment accelerated energy expenditure by about 15% and limited body weight gain by about 50%. However, in the obese animals the GC-24-mediated reduction in body weight gain dropped to only 20%, while energy expenditure remained unaffected. In addition, an analysis of gene expression in the skeletal muscle, brown adipose tissue, and liver of these obese animals failed to identify a conclusive GC-24 transcriptome footprint. Conclusion: Feeding a high-fat diet impairs most of the beneficial metabolic effects associated with treatment with TRβ-selective agonists. © 2010 Mary Ann Liebert, Inc.