title: Thyroid hormone receptor beta-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats.
abstract: 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.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil.
authors.forename: Cássio M
authors.initials: CM
authors.lastname: Villicev
authors.forename: Fatima R S
authors.initials: FR
authors.lastname: Freitas
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Aoki
authors.forename: Cássio
authors.initials: C
authors.lastname: Taffarel
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: Anselmo S
authors.initials: AS
authors.lastname: Moriscot
authors.forename: Miriam O
authors.initials: MO
authors.lastname: Ribeiro
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
authors.forename: Cecília H A
authors.initials: CH
authors.lastname: Gouveia
mesh_terms: D015502:Absorptiometry, Photon; D000085:Acetates / Q000627:therapeutic use*; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010636:Phenols / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D037042:Thyroid Hormone Receptors beta / Q000819:agonists* / Q000378:metabolism; D014284:Triiodothyronine / Q000627:therapeutic use
chemical_list: D000085:Acetates; C413355:GC 1 compound; D010636:Phenols; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine