or chylomicrons as these particles are
metabolized by LPL in peripheral tissues.
These metabolic functions of HDLs
result in these particles carrying out a cycle
known as reverse cholesterol transport, in
which HDLs pick up excess free cholesterol
from tissues and convert it to cholesterol
ester (Fielding and Fielding, 1995). The
HDL particles thus enlarge and grow less
dense as their content of cholesterol esters
increases. The HDLs then transfer
cholesterol esters to the liver for conver-
sion into bile acids (the only route for
excretion of cholesterol from the body),
and the now smaller HDLs can return to
repeat the cycle (Fig. 5.2). Clearance of
HDL particles occurs in liver and bone.
The basic scheme of lipoprotein
metabolism as just discussed exhibits
many species variations (Hollanders et al.,
1986). Pigs have high concentrations of
LDLs, similarly to humans, and are often
used as models of human lipoprotein
metabolism. In horses and ruminants,
HDLs are the predominant lipoproteins
and serve to deliver cholesterol to steroido-
genic tissues (liver, ovary, adrenals, testis)
and to a variety of tissues for membrane
synthesis. Many of the functions that LDLs
play in transport of cholesterol esters in
humans and rabbits are replaced by HDLs
in ruminants and horses. In ruminants,
there is considerable overlap in the density
range of LDLs and HDLs, which makes
separation by traditional ultracentrifugal
methods difficult (Bauchart, 1993).
Lipid Synthesis and Mobilization
Lipid synthesisLipogenesis
Lipogenesis (lipid synthesis) refers in the
strictest sense to synthesis of fatty acids
and not to the esterification of those fatty
acids to glycerides. Adipose tissue is the
main site of lipogenesis in non-lactating
cattle, sheep, goats, pigs, dogs and cats
(Beitz and Nizzi, 1997). In poultry,
similarly to humans, the liver is the major
site of lipogenesis, while in rodents (rats
and mice) both liver and adipose tissue are
important lipogenic sites. The mammary
gland of lactating farm animals actively
synthesizes fatty acids.
De novo lipogenesis occurs in the
cytosol and is a sequential cyclical process
in which acetyl (2-carbon) units are added
successively to a ‘primer’ or initial starting
molecule, usually acetyl-CoA but also
3-hydroxybutyrate in the lactating mam-
mary gland of ruminants. The source of the
acetyl units is acetyl-CoA, derived either
from glucose through glycolysis in non-
ruminants or pre-ruminants, or from
acetate via rumen fermentation of dietary
carbohydrates in ruminants. In functioning
ruminants, glucose is not used for fatty
acid synthesis, which serves to spare
glucose for other essential functions.
The nature of the mechanism that
minimizes lipogenic use of glucose by
ruminants remains unclear. Since the
discovery that activities of ATP-citrate
lyase and NADP-malate dehydrogenase
were lower in bovine adipose tissue than
in liver and adipose tissue of rats (Hanson
and Ballard, 1967), it was believed that
these enzymes limited lipogenic use of
glucose by ruminants. However, subse-
quent research showed that lactate was
used by bovine adipose tissue (Whitehurst
et al., 1978) and mammary gland (Forsberg
et al., 1985) at rates similar to those of
acetate. Lactate, after being converted to
pyruvate, is metabolized similarly to
pyruvate produced from glycolysis.
Consequently, lactate also requires the
enzymes ATP-citrate lyase and NADP-
malate dehydrogenase in order to be
converted to fatty acids. The activity of
ATP-citrate lyase in bovine adipose tissue
and mammary gland, albeit lower than that
in rat tissues, is still sufficient to allow the
observed rates of lactate conversion to fatty
acids (Forsberg et al., 1985). Moreover,
ATP-citrate lyase activity is at least equal
to that of acetyl-CoA carboxylase, the rate-
limiting step in fatty acid synthesis (Beitz
and Nizzi, 1997). Probably the most likely
explanation for the low rate of incorpora-
tion of glucose into fatty acids in ruminant
adipose tissue and mammary gland is the104 J.K. Drackley