Interaction of genetic and environmental programming of the leptin system and of obesity disposition.
Possible adverse interactions between an usually inconspicuous genetic trait and early environmental factors favoring the development of obesity were investigated in rats heterozygous for the leptin receptor defect "fatty" (fa). Pups were exposed to early postnatal overfeeding by reducing litter size 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 differences in the responsiveness of +/+ and +/fa pups to "prophylactic" leptin treatment (from day 1 to 21) were observed, with +/fa females from small litters being nearly as fat and unresponsive as previously reported for normally 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 usually inconspicuous genetic trait may thus become etiologic for the development of obesity via physiological changes other than the decreased leptin binding characterizing the genetic defect.
Schmidt
I
I
Max-Planck-Institut für physiologische und klinische Forschung, W. G. Kerckhoff-Institut, D-61231 Bad Nauheim, Germany. I.Schmidt@kerckhoff.mpg.de
Schoelch
C
C
Ziska
T
T
Schneider
D
D
Simon
E
E
Plagemann
A
A
D000273:Adipose Tissue / Q000187:drug effects / Q000254:growth & development; D000704:Analysis of Variance; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D004777:Environment; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D007031:Hypothalamus / Q000378:metabolism; D016018:Least-Squares Analysis; D020738:Leptin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008098:Litter Size; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012984:Software
D002352:Carrier Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin