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.