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Title: Impaired Metabolic Effects of a Thyroid Hormone Receptor Beta-Selective Agonist in a Mouse Model of Diet-Induced Obesity
Authors: Castillo, Melany
Freitas, Beatriz C. G. [UNIFESP]
Rosene, Matthew L.
Drigo, Rafael A.
Grozovsky, Renata
Maciel, Rui M. B. [UNIFESP]
Patti, Mary Elizabeth
Ribeiro, Miriam O.
Bianco, Antonio C.
Univ Miami
Universidade Federal de São Paulo (UNIFESP)
Joslin Diabet Ctr
Univ Prebiteriana Mackenzie
Issue Date: 1-May-2010
Publisher: Mary Ann Liebert Inc
Citation: Thyroid. New Rochelle: Mary Ann Liebert Inc, v. 20, n. 5, p. 245-553, 2010.
Abstract: Background: the use of selective agonists of the thyroid hormone receptor isoform beta (TR beta) 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 TR beta agonist. GC-24 (17 ng/[g BWday] 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 TR beta-selective agonists.
ISSN: 1050-7256
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