Overnutrition during critical developmental periods is suggested to be a risk factor
for obesity and associated metabolic disorders in later life. Underlying mechanisms
are unknown. Neuropeptides are essentially involved in the central nervous regulation
of body weight. For instance, hypothalamic galanin (GAL) is a stimulator of food intake
and body weight gain. To investigate long-term consequences of early postnatal overfeeding,
the normal litter size of Wistar rats (n=10; controls) was reduced from day 3 to day
21 of life to only 3 pups per mother (small litters, SL; overnutrition). Throughout
life, SL rats displayed hyperphagia (p<0.01), overweight (p<0.0001), hyperinsulinemia
(p<0.01), impaired glucose tolerance (p<0.001), elevated triglycerides (p<0.001),
and an increased systolic blood pressure (p<0.05). In adulthood, an increase of GAL-neurons
in the arcuate hypothalamic nucleus (ARC) was found (p<0.001), positively correlated
to body weight (p<0.001). A second experiment revealed hyperinsulinemia (p<0.001)
and increased hypothalamic insulin levels (p<0.05) in SL rats during early postnatal
life. Already on day 21 of life, i.e., at the end of the critical hypothalamic differentiation
period, in SL rats the number of GAL-neurons was increased in the ARC (p<0.001), showing
a positive correlation to body weight and insulin (p<0.05). In conclusion, neonatally
acquired persisting malformation of hypothalamic galaninergic neurons, induced by
early overfeeding and hyperinsulinism, might promote the development of overweight
and syndrome X-like alterations during life.
Copyright 1999 Elsevier Science B.V.