Differentiation and metabolism of adipose tissue are modulated by thyroid hormones (THs), but relatively little is known about the metabolism of THs in this tissue. Expression of the genes for type I iodothyronine 5 0 -deiodinase (D1), leptin (LEP) and stearoyl-CoA desaturase 1 (SCD-1) was evaluated in omental (OM) and subcutaneous (SC) fat using a cohort of 70 humans. Activities of iodothyronine deiodinases (D1, D2 and D3) were assessed in a randomly selected subpopulation of 19 subjects. D1 expression was upregulated in both OM (P ¼ 0.011) and SC (P ¼ 0.003) fat of obese subjects. Concomitantly, OM (P ¼ 0.002) and SC (P ¼ 0.028) LEP expression were increased in obesity, associated with both D1 mRNA (r ¼ 0.315, P ¼ 0.014) and activity (r ¼ 0.647, P ¼ 0.023) and inversely related to SCD-1 (r ¼ À0.266, P ¼ 0.034) expression in SC fat. Also D1 (but not D2 and D3) activity was increased in OM (Bfourfold, P ¼ 0.010) and SC (Beightfold, P ¼ 0.004) fat of obese when compared with non-obese subjects and correlated in both OM (r ¼ 0.528, P ¼ 0.036) and SC (r ¼ 0.749, P ¼ 0.005) fat with body mass index. Our results document increased D1 gene expression and activity in adipose tissue of obese humans and suggest a role of 3,5,3 0 -triiodo-L-thyronine formed by D1 in response to leptin in the modulation of adipose tissue metabolism.

Thyroid status was characterized in very preterm infants (gestational age < or =32 wk; n = 61) from birth through d 14, and in infants who died within 16 d after delivery (n = 10), where it was also correlated with metabolism of iodothyronines in peripheral tissues (brain, liver, kidney, skeletal muscle, and adipose tissue). At 3 d of life, mean plasma levels of thyroxine, triiodothyronine, and TSH started to decrease, being lower in the critically ill compared with healthy premature neonates. Activities of the three iodothyronine deiodinases enzymes (type I, II, and III, respectively) were detected in all postmortem tissue samples, except for absence of the type II activity in kidney. All activities were the highest in liver and differed in other tissues. Lack of correlation between the type I activity in liver (and kidney), and plasma levels of thyroid hormones suggested that the thyroid was the primary source of circulating triiodothyronine. On the other hand, namely in brain, correlations between activity of the deiodinases and plasma hormone levels were found which suggested a complex control by thyroid hormones of their own metabolism. High activity of type III in liver, adipose tissue, and skeletal muscle demonstrated a role of these tissues in thyroid hormones degradation. Results support the view that peripheral tissues of very preterm infants are engaged in local generation of triiodothyronine, and inactivation of thyroid hormones, but do not represent a major source of circulating triiodothyronine.