Bioenergetic impact of tissue-specific regulation of iodothyronine deiodinases during nutritional imbalance

The regulation of energy homeostasis by thyroid hormones is unquestionable, and iodothyronine deiodinases are enzymes involved in the metabolic activation or inactivation of these hormones at the cellular level. T3 is produced through the outer ring deiodination of the prohormone T4, which is catalyzed by types 1 and 2 iodothyronine deiodinases, D1 and D2. Conversely, type 3 iodothyronine deiodinase (D3) catalyzes the inner ring deiodination, leading to the inactivation of T4 into reverse triiodothyronine (rT3). Leptin acts as an important modulator of central and peripheral iodothyronine deiodinases, thus regulating cellular availability of T3. Decreased serum leptin during negative energy balance is involved in the down regulation of liver and kidney D1 and BAT D2 activities. Moreover, in high fat diet induced obesity, instead of increased serum T₃ and T₄ secondary to higher circulating leptin and thyrotropin levels, elevated serum rT3 is found, a mechanism that might impair the further increase in oxygen consumption.