16p
Medical Research Society
rise was due to an increase in cholesteryl ester; unesterified cholesterol levels fell. High plasma triglyceride levels
were common early in the disease. Typically there was
no IX- or pre p-band on lipid staining of an agarose
electrophoretic strip. Immunoelectrophoresis shows a
precipitin arc with anti-z-lipoprotein antiserum in all
specimens, but in specimens taken early in the disease the
faster moving component of the IX-arc was not seen.
At all stages most plasma cholesterol and triglyceride
was found in low density lipoproteins, but during recovery the triglyceride content of these lipoproteins fell as
the cholesteryl ester rose, suggesting that there is a functional relationship between these lipids in the non-polar
core of LDL. The concentration of high density lipoproteins was low.
On analytical ultracentrifugation the high density
lipoprotein peaks showed a marked reduction in size
with a fast and slow component as has been described
in patients with familial deficiency of lecithin; cholesterol
acyltransferase (LCAT). Also large (210 A) HDL particles
were seen by electron microscopy, which tended to aggregate to form stacks as in familial LCAT deficiency.
These findings and the similarity of the chemical changes
suggest that alterations in LCAT activity play an important part in determining the nature of the changes
which have been described.
14. PHENOBARBITONE AND ETHANOL; EFFECTS
ON SERUM AND LIVER LIPIDS IN THE RAT
A. R. MARSH, H. FRASER, G. R. THOMPSON, A. BRECKENRIDGE and B. LEWIS
Departments of Chemical Pathology, Clinical Pharmacology and Medicine, Royal Postgraduate Medical School,
Hammersmith Hospital, London W120HS
Ethanol (EtOH) is a well-established cause of fatty liver
and hypertriglyceridaemia in both man and the experimental animal. It has been reported that hepatic enzyme
inducing agents, such as phenobarbitone (P-B), can
prevent the accumulation of liver lipid following acute
administration of EtOH (Koff et al., 1970, Gastroenterology, 59, 50). In man small but significant increases
in serum cholesterol (CH) and triglyceride (TG) have been
observed following phenobarbitone administration (Miller
& Nestel, 1973, Clinical Science and Molecular Medicine,
45,257) and a possible decrease in liver lipid has also been
noted (Mezey & Robles, 1974, Gastroenterology,66,248).
The present study was designed to assess the effects
on serum and liver lipids (1) acute EtOH administration,
with and without pre-treatment with P-B, and (2) chronic
administration of EtOH, with and without concurrent
administration of P-B. In the acute experiment EtOH
increased the serum CH and TG and liver TG. P-B reduced serum TG in both undosed and EtOH treated
animals but had no significant effect on liver TG in either
group. In the chronic study P-B markedly increased CH
(from 78 to 144 mg/IOO ml) and TG (from 110 to 285
mg/l00 ml) in serum but had little effect on their concentration in liver. EtOH increased liver CH (from 3'5 to
5'3 mg/g) and TG (from 17'8 to 24'2 mg/g), an effect
which was markedly enhanced by simultaneous P-B
treatment (CH 10'7, TG 113 mg/g). Serum CH and TG
levels in the ratsfed EtOH plus P-B were higher than in
those given EtOH alone and lower than in those given
P-B alone.
It is concluded that EtOH and P-B both stimulate verylow density lipoprotein (VLDL) synthesis. EtOH is
believed to do so by increasing hepatic triglyceride
synthesis. But in our chronic experiment EtOH appeared
to impair VLDL secretion while P-B appears to promote
it. In neither study did phenobarbitone exert a 'protective' effect on ethanol induced accumulation of liver
lipids.
15. METABOLIC CONSEQUENCES OF PHOSPHOLIPID
EXCHANGE BETWEEN INTRAVENOUSLY ADMINISTERED EGG LECITHIN
AND PLASMA LIPOPROTEINS
GILBERT THOMPSON and GUNNAR SIGUURDSON
Department of Medicine, Royal Postgraduate Medical
School, London W120HS
Previous studies (Thompson et al., 1974, Journal of
Clinical Investigation, 53, 80a) showed that intravenous
(i.v.) but not oral administration of a triglyceride-egg
lecithin emulsion (Intralipid) resulted in a rise in low
density lipoprotein (LDL), a decrease in the fractional
catabolic rate (FCR) of LDL protein (apoLDL) without
any increase in synthesis, and persistence of exogenous
phospholipid in plasma. Additional evidence suggested
that the rise in LDL was associated with an increase in
the oleate:linoleate ratio in LDL lecithin and cholesterol
ester, consequent on phospholipid exchange between
LDL and the oleate-rich egg lecithin component of
Intralipid. To explore this relationship a further two
volunteers each received a course of i.v. egg lecithin
(6 g daily for 5 days). LDL cholesterol rose from a mean
of 109 to 160 and apoLDL from 85 to 102 mg/IOO ml.
Preliminary studies of 12sl_apoLDL turnover indicate
that these changes were accompanied by a decrease in
FCR. Assuming that the decrease in FCR was the cause
rather than the effect of the increase in LDL pool size,
these results provide additional evidence that apoLDL
catabolism is influenced by the fatty acid composition of
the lecithin and/or cholesterol ester components of the
LDL molecule.
16. A COMPARISON OF THE LIPID AND APOLlPOPROTEIN COMPOSITION OF INTESTINAL
AND ENDOGENOUS VERY-LOW DENSITY LIPOPROTEINS IN HUMAN SERUM
RICHARD DUNGU, AKINTUNDE ONITIRI and BARRY LEWIS
Department of Chemical Pathology and Lipid Clinic,
Royal Postgraduate Medical School, Hammersmith
Hospital, London W120HS
A raised concentration of triglyceride, in plasma obtained in the fasted state, appears to be a risk factor for
ischaemic heart disease. This triglyceride is of endogenous origin, and is transported chiefly in very-low
density lipoprotein (VLDL), secreted by the liver. During
fat absorption, VLDL synthesized in the small intestine
shares with chylomicra the additional function of dietary
fat transport. It is therefore possible that intestinal VLDL