prepartum, less triacylglycerol accumulates
in the liver at the time of calving (Grum et
al., 1996). This may be an adaptation to
allow increased metabolism of fatty acids
during their extensive mobilization.
During the last decade, research has
identified specific nuclear receptors that
are activated by fatty acids and chemicals
that cause peroxisomal proliferation in
rodents. These receptors, called peroxisome
proliferator-activated receptors (PPARs), in
turn bind to specific peroxisome prolifera-
tor response elements (PPREs) located in
the regulatory region of a number of genes
whose products are associated with lipid
metabolism (Schoonjans et al., 1996).
These include long-chain acyl-CoA
synthetase; the peroxisomal enzymes acyl-
CoA oxidase and bifunctional protein; the
mitochondrial enzymes CPT-I, medium-
chain acyl-CoA dehydrogenase and HMG-
CoA synthase; and the microsomal
cytochrome P450 enzymes CYP4A1 and
CYP4A6, which catalyse -oxidation.
Furthermore, the liver fatty acid-binding
protein gene contains a PPRE. In rats, the
gluconeogenic enzymes phosphoenol-
pyruvate carboxykinase and malic enzyme
also contain PPREs in their regulatory
regions. Although limited research has
been conducted with farm animals to date,
it is attractive to speculate that the PPARs
represent a molecular mechanism that
would function to coordinate the activity
of the metabolic machinery necessary for
fatty acid metabolism with the supply of
fatty acids to tissues.
Esterification and exportEsterification is believed to ‘compete’ with
oxidation for acyl-CoA in the liver of farm
animals. The pathways for esterification of
acyl-CoA to glycerolipids in liver are
similar to those discussed earlier for
adipose tissue. In rodents, the activities of
phosphatidate phosphohydrolase and
diacylglycerol acyltransferase appear to be
increased in times of high insulin; little is
known about regulation of these enzymes
in farm animals. In dairy cows, hepatic
capacity for esterification of fatty acids is
increased around calving (Grum et al.,
1996), which may contribute to the propen-
sity of dairy cows to develop fatty livers
around the time of calving. The enzymes
glycerophosphate acyltransferase, diacyl-
glycerol acyltransferase and phosphatidate
phosphohydrolase (Fig. 5.3) are potential
regulatory sites for accumulation of triacyl-
glycerol in the liver, but data supporting
their role are inconclusive.
The general mechanisms for synthesis
and secretion of VLDLs from liver are well
known (Bauchart, 1993). Apoprotein B is
the key component whose rate of synthesis
in the rough endoplasmic reticulum is
believed to control the overall rate of VLDL
production. Lipid components that are
synthesized in the smooth endoplasmic
reticulum are added to apoprotein B as it
moves to the junction of the two compart-
ments. After being carried to the Golgi
apparatus in transport vesicles, the apopro-
teins are glycosylated. Secretory vesicles
bud off the Golgi membrane and migrate to
the sinusoidal membrane of the hepato-
cyte. The vesicles fuse with the membrane
and release the VLDLs into blood in the
space of Disse.
Ruminants and swine do not export
triacylglycerol from the liver as VLDLs as
efficiently as do poultry or laboratory
rodents. In particular, ruminants have a
very low rate of VLDL export compared
with rats, despite similar rates of esterifica-
tion of fatty acids to triacylglycerols
(Kleppe et al., 1988). Where the limitation
in VLDL synthesis or secretion resides is
unknown (Bauchart, 1993). Based on avail-
able evidence, it appears that the rate of
synthesis or assembly of VLDLs is more
likely to be limiting than is the secretory
process per se.Possible limitations include
a low rate of synthesis or a high rate of
degradation of apoprotein B, or deficient
synthesis of phosphatidylcholine or
cholesterol.
The rate of export of triacylglycerol
from the liver corresponds in general to the
relative rate of de novofatty acid synthesis
among species, with species such as cattle
and pigs that do not synthesize fatty acids112 J.K. Drackley