Thyroid hormone receptor β-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 b (TRb)-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 mg/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 w20% 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.

Double disruption of α2A- and α2C -adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype

“…It is important to consider that lean mass by DXA is determined by the content of proteins, water, glycogen, and minerals that are not from bone. (28) In fact, we detected increased dry mass in two of the five skeletal muscles evaluated. In addition, we found increased water content in the gastrocnemius and rectus femoris.…”

“…(28) The animals were subject to a basal scan and to a scan every 4 weeks. The bone regions analyzed were the hind body, which includes the lumbar spine, pelvis, and hind limbs; the lumbar vertebrae (L 1 -L 6 ); and both femurs and tibias.…”

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

“…Treatment of rats with 3 mg T 3 /100 g body weight and equimolar amounts of GC1 (3 mg GC1/100 g body weight) resulted in a similar loss of fat mass. At variance with T 3 , which caused a loss of muscle mass, GC1 had no muscle wasting effect (181).…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…Indirect calorimetry can be studied over 30-120 minutes with reliable results (597,598,603,604). Stress might be a significant factor in these short-term studies and care should be taken to avoid or at least control for such a variable.…”