consuming a meal containing fat, the blood undergoes a transient
increase in lipids, particularly triacylglycerols, lasting several
hours. This is known as postprandial lipemia. Individuals consuming
a typical Western diet spend approximately 18 hours per day in
Exogenous fat transport begins in the intestine where dietary
fats are packaged into lipoprotein particles called chylomicrons.
Chylomicrons enter the bloodstream and deliver their triglyceride
to adipose tissue and muscle. The remnant of chylomicrons is
removed from the circulation by the liver.
Endogenous fat transportation begins when the liver secretes
a Very Low Density Lipoprotein particle (VLDL). When a VLDL particle
reaches the capillary of muscle or adipose tissue, its triglyceride
is extracted, leaving an Intermediate Density Lipoprotein (IDL).
Half of the IDL particles are removed from circulation by the
liver within two to six hours of their formation. The remaining
IDL transforms into Low Density Lipoproteins (LDL) which circulate
for approximately two and a half days before binding to LDL receptors
in the liver and other tissues.
Small dense low density lipoprotein (LDL) are more atherogenic
that larger LDL particles because they are
- more easily enter the vessel wall
- more prone to oxidative modification
- bind more tightly to the arterial wall
- cleared more slowly
The composition of triglyceride-rich lipoproteins (TRLs) are
metabolically linked to LDL. LDL particle size is primarily affected
by the plasma TG levels. Postprandial hyperlipidemia is associated
with an increase in the proportion of small, dense LDL. Furthermore,
prolonged lipemia promotes the transfer of core lipids between
TRLs and high density lipoprotein (HDL) leading to a reduction
in HDL cholesterol levels. This combination is known as the lipid
triad or atherogenic lipoprotein profile:
- high plasma TG concentrations
- increased small dense LDL
- low HD
Bravo E, Napolitano M, and Botham KM (2010). Postprandial
Lipid Metabolism: The Missing Link Between Life-Style Habits
and the Increasing Incidence of Metabolic Diseases in Western
Countries? The Open Translational Medicine Journal, 2010, 2,
Elevated circulating cholesterol reduces the cells ability
to make its own cholesterol by turning off the production of
HMG CoA reductase, which interrupts a step in the biosynthetic
pathway of cholesterol. Incoming LDL derived cholesterol promotes
the storage of cholesterol in the cell by activating ACAT which
reattaches a fatty acid to excess cholesterol molecules. This
results in cholesterol esters that are deposited in storage droplets.
The accumulation of cholesterol within the cell drives a feedback
mechanism which stops the cells synthesis of new LDL receptors.
The cell adjusts its receptors, so only enough cholesterol is
brought in to supply its needs.
With Familial Hypercholesterolemia, an inherited mutant gene
causes the absence of LDL receptors. High circulating levels
of LDL are found to be caused by an increased production and
a decrease in the removal of LDL. Consequently, Familial Hypercholesterolemia
leads to high blood cholesterol and heart attacks in the young.