ADIPOSITY AND SERUM LEPTIN INCREASE IN FATTY (FA FA) BNZ NEONATES WITHOUT DECREASED VMH SEROTONERGIC ACTIVITY/

Decreased ventromedial hypothalamic (VMH) serotonergic activity occurs in genetic and diet-induced animal models of obesity. We previously f ound that this activity was lower in adult and in 12-day-old Zucker fa /fa vs. Fa/Fa pups, the fa/fa animals being identified by their greate r adiposity. In the present study, we evaluated fa/fa rats (Brown Norw ay-Zucker hybrids) at ages 2, 4, 7, and 12 days to test the hypothesis that lower VMH serotonergic activity occurs before increased adiposit y and/or attenuated energy expenditure. Our results negate this hypoth esis. VMH serotonergic activity showed no consistent genotype differen ces even at 12 days of age. In contrast, by day 7, fa/fa vs. Fa/Fa pup s had higher serum leptin concentrations, greater percent body fat, lo wer resting and cold-induced energy expenditure, and lower activity of brown fat thyroxine 5'-deiodinase, an enzyme that converts thyroxine to triiodothyronine. We conclude that the onset of increased adiposity induced by the fa gene does not require decreased VMH serotonergic ac tivity and that the lower serotonergic activity seen in older fa/fa pu ps may be secondary to metabolic consequences of the disruption of the leptin regulatory pathway.