Type I iodothyronine 5′-deiodinase mRNA and activity is increased in adipose tissue of obese subjects

Abstract

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 Function Tests in Obese Prepubertal Children: Correlations with Insulin Sensitivity and Body Fat Distribution

“…Similarly to our findings, an independent positive correlation between waist circumference and fT3 levels has been reported in obese women [19]. This result may be explained by the recent findings of Ortega et al [20], who demonstrated that the expression and activity of type I iodiothyronine 5′-deiodinase, an important source of circulating T 3 , are increased in adipose tissue from obese individuals.…”

Thyroid Hormones and the Metabolic Syndrome

“…Similarly, BAT depends on deiodinase activity but on subtype DII which in fasted conditions is dramatically upregulated. This regulation is critically dependent on the current thyroid status [22,36]. Studies in deiodinase knock-out (DII KO) animals support such notion.…”

Triiodothyronine and Free Thyroxine Levels are Differentially Associated with Metabolic Profile and Adiposity-Related Cardiovascular Risk Markers in Euthyroid Middle-Aged Subjects

“…Indeed, under conditions of increasing adiposity, a higher DIO1 activity in white adipose tissue, through stimulation by leptin has been shown in mice (45). Also in humans, Ortega et al have shown an increase in DIO1-activity in hypertrophic white adipose tissue (46).…”