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.
Marie
V
V
Institut National de la Santé et de la Recherche Médicale, Unité 177, Paris, France.
Dupuy
F
F
Bazin
R
R
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D000833:Animals, Suckling; D007328:Insulin / Q000097:blood; D007453:Iodide Peroxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism*; D014886:Weaning
D007328:Insulin; D014284:Triiodothyronine; D007453:Iodide Peroxidase; D013974:Thyroxine