Effect of age and gene dosage on brown adipose tissue of Zucker obese fa/fa rats.

Experiments were performed to investigate the effect of age and genotype on brown adipose tissue thermogenesis in Zucker rats. Specific [3H]GDP binding to interscapular brown adipose tissue mitochondria ( IBATM ) was reduced in 14-day-old preobese fa/fa rats and remained lower after weaning. A gene-dosage effect of the recessive fa gene was observed in 8- to 10-wk-old rats in both IBATM [3H]GDP binding and the thermic effect of a balanced meal (50 kJ Complan ), measured by indirect calorimetry. In each case the heterozygote (Fa/fa) group had a value intermediate between those of obese (fa/fa) and the homozygous lean (Fa/Fa) groups. Norepinephrine increased IBATM [3H]GDP binding to similar levels in lean (Fa/fa) and obese (fa/fa) rats and induced similar increases in oxygen consumption in Fa/Fa, Fa/fa, and fa/fa rats. It is concluded that the impaired, diet-related brown adipose tissue thermogenesis is closely related to the primary gene defect in the obese rat. This defect may result from misregulation of the autonomic nervous system.