Adiposity and serum leptin increase in fatty (fa/fa) BNZ neonates without decreased VMH serotonergic activity

Barbara A Horwitz, Jock S. Hamilton, Vanessa H. Routh, Kerri Green, Peter J Havel, Albert Chan

Research output: Contribution to journalArticlepeer-review


Decreased ventromedial hypothalamic (VMH) serotonergic activity occurs in genetic and diet-induced animal models of obesity. We previously found 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 greater adiposity. In the present study, we evaluated fa/fa rats (Brown Norway-Zucker hybrids) at ages 2, 4, 7, and 12 days to test the hypothesis that lower VMH serotonergic activity occurs before increased adiposity and/or attenuated energy expenditure. Our results negate this hypothesis. VMH serotonergic activity showed no consistent genotype differences even at 12 days of age. In contrast, by day 7, fa/fa vs. Fa/Fa pups had higher serum leptin concentrations, greater percent body fat, lower 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 activity and that the lower serotonergic activity seen in older fa/fa pups may be secondary to metabolic consequences of the disruption of the leptin regulatory pathway.

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Issue number6 PART 1
StatePublished - 1998


  • Brown adipose tissue
  • Brown norway-zucker rats
  • Energy expenditure
  • Genetic obesity
  • Thyroxine 5'-deiodinase
  • Uncoupling protein
  • Ventromedial hypothalamus

ASJC Scopus subject areas

  • Physiology (medical)


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