TRbeta activation prevents obesity

Thyroid hormone rapidly increases energy expenditure whilst reducing serum cholesterol and triglycerides when given to animals and humans. However its clinical use as vehicle for weight loss is limited due to several side effects such as cardiac arrhythmia, bone loss, nervousness and anxiety. One approach to maximise its benefits would be to use thyroid hormone analogues capable of tissue specificity either by selective uptake and/or by selective binding to the two thyroid hormone receptors (TR) isoforms α and β.

Amorim and colleagues studied the influence of the TRβ selective agonist, GC-24, on the response of rats to a high calorie diet for one month. GC-24 treatment with a high fat diet reduced adiposity, improved insulin sensitivity, and accelerated resting metabolic rate. Key BAT metabolic enzymes were induced by GC-24 treatment, whilst only minimally affecting the liver, skeletal muscle and white adipose tissue. The study identified a potential mechanism for the weight loss previously reported with some thyroid hormone analogues and has important therapeutic implications. A key feature of GC-24 is the absence of an effect on the heart. Amorim, B et al, Journal of Endocrinology, DOI:10.1677/JOE-08-0539