Among the endocrine factors able to regulate energy metabolism and body weight, thyroid hormones (THs)
play important roles. 3,5,3'-triiodothyronine (T3) increases metabolic rate and leads to cholesterol reduction and loss of
body weight and adiposity by increasing respiration and energy expenditure and by lowering metabolic efficiency. Because
of these effects, T3 was previously tested as an anti-obesity and hypolipidemic agent. However, due to undesirable
side effects, particularly within the cardiovascular system, its use was discontinued. The development of TH derivatives
that retain lipid-lowering and anti-obesity efficacy while lack cardiovascular side effects would represent a potentially
valuable therapeutic tool for the reduction of some important risk factors. Many laboratories have demonstrated metabolic
effects of 3,5-diiodo-L-thyronine (3,5-T2), a natural TH, which can mimic biologic effects of T3 without inducing thyrotoxicosis
effects. Recent studies revealed that 3,5-T2 acted as a protective/ameliorative factor against diet-induced obesity
and its associated metabolic derangements (liver steatosis, hypertrigliceridemia, hypercholesterolemia, and insulin resistance).
Accumulating evidence suggests that the actions of 3,5-T2 are exerted through mechanisms independent of those
actuated by T3 and do not involve TH receptors. Instead, 3,5-T2 exerts marked effects on energy metabolism by acting
mainly at the mitochondrial level.
Keywords: 3, 5-diiodo-L-thyronine, AMP-activated protein kinase, cholesterol, energy metabolism, fatty acids, insulin resistance,
liver, mitochondria, obesity, sirtuins, steatosis, thyroid hormone.
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