Alteration of SREBP activation in liver of trisomy 21 fetuses

We previously reported that trisomy 21 (T21) fetuses have an intrinsic lipi d metabolism abnormality resulting in higher serum cholesterol levels than their matched controls. In an attempt to clarify the biochemical basis of t his derangement we analyzed the liver cholesterol levels and activation of the sterol regulatory element binding proteins SREBP-1 and SREBP-2. We repo rt here for the first time that SREBP-1 and SREBP-2 are present in human fe tal liver and their activation follows a different regulatory pattern. More over T21 fetuses show a peculiar pattern of SREBP activation which, at vari ance from control fetuses, involves sterol-independent maturation of SREBP- 1. Multiple defects accompanied the lipid derangement in T21, resulting in high circulating and tissue cholesterol. This may serve as an early biochem ical marker of an unknown, possibly genetically determined mechanism, whose consequence on lipid homeostasis during postnatal and adult life is still not understood. (C) 1999 Academic Press.