A TRβ-selective agonist confers resistance to diet-induced obesity

Beatriz S. Amorim, Cintia B. Ueta, Beatriz C.G. Freitas, Renata J. Nassif, Cecília Helena De Azevedo Gouveia, Marcelo A. Christoffolete, Anselmo S. Moriscot, Carmen Lucia Lancelloti, Flávia Llimona, Hermes Vieira Barbeiro, Heraldo Possolo De Souza, Sergio Catanozi, Marisa Passarelli, Marcelo S. Aoki, Antonio C. Bianco, Miriam O. Ribeiro

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Abstract

Thyroid hormone receptor β (TRβ also listed as THRB on the MGI Database)-selective agonists activate brown adipose tissue (BAT) thermogenesis, while only minimally affecting cardiac activity or lean body mass. Here, we tested the hypothesis that daily administration of the TRβ agonist GC-24 prevents the metabolic alterations associated with a hypercaloric diet. Rats were placed on a high-fat diet and after a month exhibited increased body weight (BW) and adiposity, fasting hyperglycemia and glucose intolerance, increased plasma levels of triglycerides, cholesterol, nonesterified fatty acids and interleukin-6. While GC-24 administration to these animals did not affect food ingestion or modified the progression of BW gain, it did increase energy expenditure, eliminating the increase in adiposity without causing cardiac hypertrophy. Fasting hyperglycemia remained unchanged, but treatment with GC-24 improved glucose tolerance by increasing insulin sensitivity, and also normalized plasma triglyceride levels. Plasma cholesterol levels were only partially normalized and liver cholesterol content remained high in the GC-24-treated animals. Gene expression in liver, skeletal muscle, and white adipose tissue was only minimally affected by treatment with GC-24, with the main target being BAT. In conclusion, during high-fat feeding treatment with the TRβ-selective agonist, GC-24 only partially improves metabolic control probably as a result of accelerating the resting metabolic rate.

Original languageEnglish (US)
Pages (from-to)291-299
Number of pages9
JournalJournal of Endocrinology
Volume203
Issue number2
DOIs
StatePublished - Nov 1 2009

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Amorim, B. S., Ueta, C. B., Freitas, B. C. G., Nassif, R. J., Gouveia, C. H. D. A., Christoffolete, M. A., Moriscot, A. S., Lancelloti, C. L., Llimona, F., Barbeiro, H. V., De Souza, H. P., Catanozi, S., Passarelli, M., Aoki, M. S., Bianco, A. C., & Ribeiro, M. O. (2009). A TRβ-selective agonist confers resistance to diet-induced obesity. Journal of Endocrinology, 203(2), 291-299. https://doi.org/10.1677/JOE-08-0539