Thyroid hormone receptor b (TRb 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 TRb 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, nones- terified fatty acids and interleukin-6. While GC-24 admin- istration 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 TRb-selective agonist, GC-24 only partially improves metabolic control probably as a result of accelerating the resting metabolic rate.

A TRb-selective agonist confers resistance to diet-induced obesity.

Beatriz S Amorim, Cintia B Ueta, Beatriz C G Freitas, Renata J Nassif, Cecılia Helena de Azevedo Gouveia, Marcelo A Christoffolete, Anselmo S Moriscot, Carmen Lucia Lancelloti, Flavia Llimona, Hermes Vieira Barbeiro, Heraldo Possolo de Souza, Sergio Catanozi, Marisa Passarelli, Marcelo S Aoki, Antonio C Bianco and Miriam O Ribeiro. Journal of Endocrinology. 26 August, 2009. doi: 10.1677/JOE.08-0539

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