Introduction to Human Nutrition

(Sean Pound) #1
Nutrition and Metabolism of Lipids 97

In the small intestine, the newly re-esterifi ed TAGs
and CEs associate with specifi c amphipathic proteins
and phospholipids in the enterocyte to form the
largest and most TAG-rich lipoproteins, known as
chylomicrons. The enterocyte is capable of synthesiz-
ing three different apoproteins (apo): apoA-I, apoA-
IVs and apoB (B-48). The last apoprotein is expressed
in two isoforms, the arbitrarily named apoB-100,
which is synthesized in the liver, and a shorter relative
of B-100, which is produced by the enterocyte and is
approximately 48% of the size of B-100 and thus
appropriately named apoB-48. While both apopro-
teins are products of the same gene, the mRNA
undergoes post-transcriptional editing in the entero-
cyte to produce a truncated polypepetide. ApoB-48 is
produced in the rough endoplasmic reticulum and
transferred to the smooth endoplasmic reticulum,
where it combines with a lipid droplet, or nascent
chylomicron, and then migrates to the Golgi appara-
tus. Here, the apoproteins (A-I, A-IV, and B-48) are
glycosylated before the chylomicrons eventually leave
the enterocyte by exocytosis through the basement
membrane, across the intracellular space between the
enterocyte and the lacteal, and are fi nally discharged
into the lymphatic vessels.


Postprandial lipemia


The turbidity or milkiness of serum or plasma follow-
ing the ingestion of fat marks the arrival of dietary fat
now contained in chylomicrons in the blood. The
milky appearance of plasma or serum after the inges-
tion of fat arises from the chylomicrons, which are of
a suffi cient size physically to scatter light and create
the milky appearance of serum or plasma after a meal.
The size and composition of the chylomicrons pro-
duced after a fatty meal are determined by the fat
content of the meal. Hence, the nature of fatty acids
in chylomicron TAG refl ects the nature of fatty acid
in the meal. Each chylomicron particle carries a single
molecule of apoB-48 which, unlike its other smaller
counterparts A-I and A-IV, remains with the chylomi-
cron throughout its life in the circulation. There is
little evidence to suggest that the production of apoB-
48, and thus the number of particles, increases in
response to an increased fl ux of dietary fat. Instead,
the enterocyte incorporates more TAG into each chy-
lomicron and expands the size of each chylomicron
to facilitate the transport of larger amounts of
absorbed dietary fat. There is evidence to suggest that


chylomicrons containing lipids enriched with poly-
unsaturated fatty acids (PUFAs) are larger than
chylomicrons enriched with saturated fat, since the
former occupy more space when packaged into a lipo-
protein. This has implications for the subsequent
metabolism and fate of these lipoproteins in the cir-
culation, since TAGs associated with larger chylomi-
crons are known to be hydrolyzed more rapidly. It is
thought that apoB-48 is produced continuously in the
enterocyte-forming pools of apoB-48 in readiness for
the sudden reception of dietary fat and production of
chylomicrons. Nevertheless, small chylomicrons can
be detected throughout the postabsorptive phase.
The onset, duration, and magnitude of postpran-
dial lipemia can be monitored in the laboratory after
a standard fat-containing meal by making serial mea-
surements of serum TAG or more specifi cally TAG
associated with TAG-rich lipoproteins over a post-
prandial period of up to 8 or 9 hours (remnants of
chylomicrons can be detected 12 hours after a meal).
Alternatively, the levels of apoB-48 or retinyl esters in
serum act as useful markers or tracer molecules
for following the metabolism of chylomicrons in
the postprandial period. In normal subjects postpran-
dial lipemia peaks between 3 and 4 hours and sub-
sides to baseline concentration after 5–6 hours. In
some cases, postprandial TAG (mainly in chylomi-
crons) can appear in the blood within 30 min and
peak as early as 1 hour after the ingestion of fat. So
rapid is this rise in TAG that it is believed to represent
preformed lipid in the enterocyte from the previous
meal that is shunted into the circulation by the incom-
ing fat load. Note that, in addition to the time taken
to emulsify, hydrolyze, and absorb dietary fat, re-
esterifi cation of TAG in the enterocyte and lipopro-
tein assembly alone takes about 15 min, although
shunting means that the fi rst TAG can appear within
30 min, with the fi rst peak after 1 hour. This shunting
phenomenon is particularly noticeable during the day
and gives rise to two or even more peaks, whereas
postprandial peaks following an overnight fast are
usually monophasic.
Chylomicrons are not the only TAG-rich lipopro-
teins in the postprandial phase. Chylomicrons clearly
contribute signifi cantly to the extent of postprandial
lipemia, and the rate at which the TAGs in these lipo-
proteins are hydrolyzed is known to be a critical deter-
minant of the extent and time-course of postprandial
lipemia. The TAGs in circulating chylomicrons are
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