Long-chain free fatty acids (FA) were shown to exert a regulatory func
tion in the nucleus. However, the route of their entry remains uncerta
in. The aim of the present study was to examine whether the extracellu
lar FA enter the hepatocellular nuclei. The experiments were carried o
ut in vivo and in vitro. Intravenous administration of albumin-bound [
C-14]-palmitic and [C-14]-linoleic acid resulted in rapid accumulation
of the labels in the nuclear lipids. Unesterified [C-14]-palmitic aci
d represented 22.4 +/- 1.7 and [C-14]-linoleic acid 17.6 +/- 1.3 perce
nt of the total lipid radioactivity. In vitro, confocal laser scanning
microscopy was used to examine 12-NBD-stearate (a fluorescent derivat
ive of stearate) translocation into the nuclei of isolated hepatocytes
. It was found that 12-NBD stearate enters the nucleus and that this u
ptake depends on the extracellular and/or cytoplasmic concentration. I
t is concluded that factors (e.g. dietary) leading to alterations in t
he plasma FA composition and content can result in rapid changes of th
e nuclear FA pool and thus regulate certain nuclear processes.