A 25-year-old female was referred to a lipid research center for inves-
tigation of moderate hypertriglyceridemia because the plasma lipid and
lipoprotein profiles showed abnormalities. Both HDL and LDL were
more buoyant and showed elevations in TG content with the mass of
TG approximately the same as that of cholesterol. A deficiency in
which of the following is the most likely cause of this patient’s lipid
A. Lecithin-cholesterol acyltransferase (LCAT)
B. Lipoprotein lipase
C. Apoprotein C-II
D. Hepatic lipase
E. Apoprotein B-100
A nsw ers
A. This patient presents with classical symptoms of hypertriglyc-
eridemia: milky plasma, eruptive xanthomas, enlarged liver and
spleen, and symptoms of pancreatitis. The milky plasma is due to
abnormally high chylomicron levels, indicating that TG is not being
removed from the transporter of dietary TG and it is accumulating in
the plasma. The other lipoproteins listed have low levels of TG, are
much smaller, and would not be expected to lead to milky plasma if
C. Decreased lipoprotein lipase activity is the result of the failure of
the pancreatic P-cells to produce and secrete insulin. Insulin stimu-
lates the synthesis of lipoprotein lipase; in the absence of insulin,
lipoprotein lipase activity in the capillary beds is low. While a defi-
ciency in apoC-II would also lead to hypertriglyceridemia, this
genetic defect is rare. If a Type I diabetes mellitus patient is not given
insulin, the increased glucagon/insulin ratio would stimulate gluco-
neogenesis and P-oxidation in the liver rather than synthesis of
triglycerides. Neither a deficiency of LDL receptors nor hormone-
sensitive lipase would be expected to increase circulating TG levels.
D. Hepatic lipase. The abnormal buoyancies of the LDL and HDL
fractions due to their increased TG content indicate that IDL is not
being processed to LDL and HDL is not being remodeled. Both of
these processes are accomplished by hepatic lipase. A deficiency in
LCAT would lead to elevated serum cholesterol levels, almost all as
free cholesterol. Deficiencies in lipoprotein lipase or apoC-II would
lead to hypertriglyceridemia as increased chylomicrons and/or
VLDL. An apoB-100 deficiency would lead to increased levels of
LDL, but they would have the normal TG/cholesterol ratio.
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