Decreased T4-to-T3 conversion in brown adipose tissue of Zucker fa/fa pups before the onset of obesity.

To determine whether the capacity of thyroxine (T4)-to-3,5,3'-triiodothyronine (T3) conversion was altered in Zucker fa/fa pups, we measured thyroxine 5'-monodeiodinase (T(4)5'D) activity in brown adipose tissue (BAT) and liver of suckling and weaned fa/fa and Fa/fa littermates. In suckling fa/fa compared with Fa/fa rats, T(4)5'D was reduced by 30-55% in BAT and slightly increased in liver, while serum free T3 was significantly decreased (-30%). Altered T(4)5'D activity in BAT of fa/fa pups could be corrected by adrenergic stimulation. After weaning, in fa/fa rats, the capacity for T4-to-T3 conversion was totally restored in BAT while it was dramatically reduced in liver. The concentration of serum free T3 remained lower in fa/fa than in Fa/fa rats (-40%). These data confirm that BAT is a very early site of fa gene expression and are consistent with the hypothesis that a defect in the autonomic nervous system may be a primary cause of this genetic obesity. It is also suggested that, during suckling, BAT plays an important role in systemic production of T3.