Metabolic effects of 3,5-Diiodo-L-Thyronine

Thyroid hormones have been proposed as anti obesity drugs due
to their effects on basal metabolism and the ability to increase energy
expenditure. However, their clinical use has been strongly
curbed by the concomitant onset of thyrotoxicosis. In this setting,
several studies have been undertaken to assess the role of 3,5 diiodo-
L-thyronine (T2), an endogenous metabolite of thyroid hormone
derived from the enzymatic deiodination of triodothyronine T3. The
metabolic effects of T2 are similar to those induced by T3.
However, these effects appear to involve different and not welldefined
mechanisms that make this molecule clinically useful as
potential drug in the treatment of pathological conditions such as
obesity and hepatic steatosis. The main pharmacological target of
T2 appears to be the mitochondria. Therefore, the administration of
T2 to obese subjects might improve the mitochondrial performance,
which is generally recognized to be reduced in these subjects who
must oxidize greater quantities of substrates. In this context, it can
be hypothesized that T2, by acting mainly on mitochondrial function
and oxidative stress, might be able to prevent and revert the tissue
damages and hepatic steatosis induced by a hyperlipidic diet and
a concomitant reduction in the circulating levels LDL and triglycerides
as well. This review the discuss the mechanisms of action of
T2 and the possible, future clinical uses of T2 analogs for the treatment
lipid dysmetabolism related to obesity and overweight.