Litter size, adrenalectomy and high fat diet alter hypothalamic monoamines in genetically lean (Fa/Fa) Zucker rats

To determine if diet-induced obesity is associated with depressed serotonergic activity (as is genetic obesity), we examined hypothalamic biogenic amines in 11-wk-old genetically lean (Fa/Fa) male Zucker rats raised in small (3 pups/dam) or control (8-9 pups/dam) litters. Five-week-old rats were adrenalectomized or sham-operated and, 1 wk later, fed either 11% of energy as fat (low fat) or 68% of energy as fat (high fat) diets for 5 wk. Tissue punches from the ventromedial nucleus (VMN), the paraventricular nucleus and the preoptic area were assayed via HPLC. Rats fed high vs. low fat had a greater percentage of body fat and brown fat mitochondrial GDP binding, whereas serotonergic turnover was lower. Small litter vs. control litter animals had lower VMN and preoptic concentrations of 3,4- dihydroxyphenylacetic acid, a major metabolite of dopamine. Although adrenalectomy resulted in smaller, leaner rats, it did not differentially affect the rats that became fatter. Because VMN and preoptic dopaminergic activities were depressed in small litter vs. control litter rats but the percentage of body fat was unchanged, this decreased dopamine metabolism is probably not causal to the obesity development. However, the same cannot be said for the attenuated serotonergic activity, although such activity may not be directly related to the degree of obesity.