Aerobic exercise in combination with calorie restriction decrease tissue expression of type I deiodinases and this negatively affects metabolic rate. In contrast, resistance training stimulates protein synthesis and this increases metabolic rate.
Deiodinases are enzymes responsible for the metabolism of thyroid hormones. Three categories of deiodinases exist, type I, type II and type III. These enzymes are present in tissues in different concentrations where they control the local metabolism of centrally released thyroid hormones. Type I and type II deiodinases increase metabolism in cells because they convert tetraiodothyronine (T4, thyroxine) to triiodothyronine (T3). Thyroid receptors in the nucleus of cells bind T3 with an affinity much higher than that of T4. As a result most of the biological activity (~90 %) results from the action of T3. In contrast, type III deiodinases convert T4 to an inactive form of thyroid hormone called reverse T3. By regulating the gene expression of deiodinases in the cells, the body can modify the metabolic rate of tissues. Environmental factors that affect the expression of these enzymes can therefore change metabolic rate irrespective of the amount of circulating thyroid hormones.
Forced calorie restriction diet do not cause long term successful weight loss. One of the reasons for this is that they result in muscle loss and a down regulation of metabolic rate. The presence of a diminished metabolic rate following several weeks of forced calorie restriction, coupled to the appetite stimulatory effects of the hypothalamus greatly increases the risk of weight regain following resumption of normal eating. At the local level, the reduction in metabolic rate seen during forced calorie restriction diets is controlled by the deiodinase enzymes. In fact, forced calorie restriction is known to downregulate expression of the type I deiodinase enzymes, thus diminishing the metabolic activity in certain tissues including skeletal muscle and liver. Reduced peripheral conversion of T4 to the more active T3 is seen during weight loss. Because type I deiodinases are also reduced as a response to stress, aerobic exercise combined with forced calorie restriction likely further down regulates the expression of the type I deiodinase enzyme.
Because circulating thyroid hormone levels do not reflect the thyroid hormone activity in tissue, measurement of circulating levels is misleading. For this reason an individual can have normal or even raised levels of plasma thyroid stimulating hormone (TSH) and yet still have diminished metabolism in tissues. While T3 levels in the plasma may drop during forced calorie restriction, the magnitude of the reduction is always far less than that displayed by peripheral tissue because the type II deiodinase enzymes in the pituitary gland are not downregulated to the same extent as the type I deiodinase enzymes in peripheral tissue in response to forced calorie restriction or stress. A small drop in plasma T3 therefore likely reflect a large drop in the peripheral tissue concentrations of T3. Of course in a clinical setting tissue levels of T3 cannot be measured, and doctors usually rely on thyroid stimulating hormone or T4 concentrations within plasma. However, neither of these will be an accurate representation of the true metabolic rate.
The type III deiodinase is only present in peripheral tissue, but expression is increased in response to stress which may include forced calorie restrictive diets in combination with exercise. Tissue concentrations of reverse T3 therefore increase under such conditions. Because reverse T3 is able to bind to the same receptors as normal T3, even small increases of reverse T3 can significantly reduce the amount of T3 that bonds to intracellular receptors. In addition reverse T3 may inhibit the amount of T3 that is transported into the cell because of the affinity of the reverse T for the same transport proteins. Further, reverse T3 may bind to type I deiodinase enzymes and this may decrease cellular production of T3. Leptin resistance, a condition seen with development of the metabolic syndrome can result in a suppression of type I deiodinase activity and an upregulation of type III deiodinase activity. Evidence shows that reversal of leptin resistance may restore correct deiodinase activity and thus upregulate peripheral metabolism1.
