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Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
1 School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
2 Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
3 Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
4 Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
5 Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
(Requests for offprints should be addressed to C H A Gouveia; Email: cgouveia{at}usp.br)
It is well known that thyroid hormone affects body composition; however, the effect of the thyroid hormone receptor ß (TRß)-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 µg/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 ~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.
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