Low replacement doses of thyroxine during food restriction restores type 1 deiodinase activity in rats and promotes body protein loss.

During food restriction, decreased basal metabolic rate secondary to reduced serum thyroid hormones levels contributes to weight loss resistance. Thyroxine (T(4)) and 3,3',5-tri-iodothyronine (T(3)) administration during caloric restriction produce deleterious side effects; however, the administration of physiological doses of T(4) during food restriction has never been evaluated. The aim of this study was to analyze the effects of low replacement doses of T(4) in Wistar rats subjected to 40% food restriction. Food restriction for 30 days led to significantly reduced liver type 1 deiodinase activity, serum TSH, leptin, T(4), T(3), metabolic rate, and body mass. The significant reduction in hepatic deiodinase activity found during food restriction was normalized in a dose-dependent manner by T(4) replacement, showing that decreased type 1 deiodinase (D1) activity is secondary to decreased serum thyroid hormone levels during caloric restriction. The lowest replacement dose of T(4) did not normalize resting metabolic rate, but was able to potentiate the effects of food restriction on carcass fat loss and did not spare body protein. The highest dose of T(4) produced a normalization of daily oxygen consumption and determined a significant reduction in both carcass fat and protein content. Our results show that serum T(4) normalization during food restriction restores serum T(3) and liver D1 activity, while body protein is not spared. Thus, decreased serum T(4) during caloric restriction corresponds to a protective mechanism to avoid body protein loss, highlighting the importance of other strategies to reduce body mass without lean mass loss.