Thyroid hormone receptor beta-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats.

It is well known that thyroid hormone affects body composition; however, the effect of the thyroid hormone receptor beta (TRbeta)-selective thyromimetic GC-1 on this biological feature had not been demonstrated. In the current study, we compared the effects of a 6-week treatment with triiodothyronine (T3; daily injections of 3 or 6 microg/100 g body weight) or GC-1 (equimolar doses) on different metabolic parameters in adult female rats. Whereas all animals gained weight (17-25 g) in a way not basically affected by T3 or GC-1 treatment, only T3 treatment selectively increased food intake (50-70%). Oxygen consumption was significantly and equally increased (50-70%) by T3 and GC-1. Analysis of body composition by dual-energy X-ray absorptiometry (DEXA) revealed that, whereas control animals gained about 80% of fat mass, T3- or GC-1-treated animals lost 70-90 and approximately 20% respectively. Direct analysis of the carcass showed that T3 treatment promoted a 14-74% decrease in fat content but GC-1 treatment promoted only a 15-23% reduction. The gain in lean mass by DEXA and the carcass protein content were not affected by T3 or GC-1 treatment. However, the mass of individual skeletal muscles was negatively affected by T3 but only barely by GC-1. These findings highlight the potential use of GC-1 for the treatment of obesity and the metabolic syndrome.
AuthorsCássio M Villicev, Fatima R S Freitas, Marcelo S Aoki, Cássio Taffarel, Thomas S Scanlan, Anselmo S Moriscot, Miriam O Ribeiro, Antonio C Bianco, Cecília H A Gouveia
JournalThe Journal of endocrinology (J Endocrinol) Vol. 193 Issue 1 Pg. 21-9 (Apr 2007) ISSN: 0022-0795 [Print] England
PMID17400799 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acetates
  • GC 1 compound
  • Phenols
  • Thyroid Hormone Receptors beta
  • Triiodothyronine
  • Absorptiometry, Photon
  • Acetates (therapeutic use)
  • Adipose Tissue (drug effects)
  • Animals
  • Body Composition (drug effects)
  • Energy Metabolism (drug effects)
  • Female
  • Heart (drug effects)
  • Muscle, Skeletal (drug effects)
  • Obesity (drug therapy, metabolism)
  • Organ Size (drug effects)
  • Oxygen Consumption (drug effects)
  • Phenols (therapeutic use)
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Thyroid Hormone Receptors beta (agonists, metabolism)
  • Triiodothyronine (therapeutic use)

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