I. Schmidt et al., Interaction of genetic and environmental programming of the leptin system and of obesity disposition, PHYSIOL GEN, 3(2), 2000, pp. 113-120
Possible adverse interactions between an usually inconspicuous genetic trai
t and early environmental factors favoring the development of obesity were
investigated in rats heterozygous for the leptin receptor defect "fatty"( f
a). Pups were exposed to early postnatal overfeeding by reducing litter siz
e from normally 10-12 to only 4. Rearing +/+ and +/fa pups from day 3 to 21
in small litters increased fat-free dry mass and body fat, but only in the
latter did a significant interaction with genotype occur. Pronounced diffe
rences in the responsiveness of +/+ and +/fa pups to "prophylactic" leptin
treatment (from day 1 to 21) were observed, with +/fa females from small li
tters being nearly as fat and unresponsive as previously reported for norma
lly reared fa/fa pups. Clear heterozygous differences in total hypothalamic
leptin binding, but no litter size effect, paralleling the differences in
leptin responsiveness, were observed. By early postnatal overfeeding an usu
ally inconspicuous genetic trait may thus become etiologic for the developm
ent of obesity via physiological changes other than the decreased leptin bi
nding characterizing the genetic defect.