Triglyceride-Production Rates in Patients With Type-Iv Hypertriglyceridæmia

Kaye, Josse; Galton, D. J.

doi:10.1016/s0140-6736(75)91948-0

Cited by 14 publications

(4 citation statements)

References 12 publications

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“…3, plasma triglyceride levels were inversely correlated with LPL activity (r = -0.686, P < 0.01, n = 30), while HDL cholesterol levels were positively correlated with the activity of the enzyme (r = 0.678, P < 0.01 ). To further demonstrate that the increase in LPL activity elevated HDL cholesterol levels directly, an experiment was performed in which protamine sulfate was used to block the rise in LPL activity ( 17) in response to administration of NO-1886. Prior intravenous protamine sulfate, 25 mg dissolved in saline/kg BW, inhibited both the rise in HDL cholesterol and the fall in plasma triglyceride levels, both of which were always induced by the compound (Table III).…”

Section: Resultsmentioning

confidence: 99%

The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis.

Tsutsumi¹,

Inoue²,

Shima³

et al. 1993

J. Clin. Invest.

141

103

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We have discovered a novel compound, NO-1886, which possesses a powerful lipoprotein lipase (LPL) activity-increasing action. Administration of NO-1886 increased LPL activity in the postheparin plasma, adipose tissue, and myocardium of rats, and produced a reduction in plasma triglyceride levels with concomitant elevation ofHDL cholesterol levels. Administration of NO-1886 increased LPL enzyme mass in postheparin plasma and mRNA activity in epididymal adipose tissue, and it was concluded that the mode of action of this compound is stimulation of tissue LPL synthesis. We also conducted longterm studies to assess the impact of increases in LPL activity and HDL levels on the development of atherosclerotic lesions in rats. Administration of NO-1886 for as long as 90 d significantly decreased the degrere of atherosclerotic changes in the coronary arteries of vitamin D2-treated, cholesterol-fed rats. Statistical analysis indicated that increased concentration of HDL is the factor contributing mostly to the prevention ofcoronary artery sclerosis. In summary, the results of our study indicate that compound NO-1886 increases LPL activity, causing an elevation in HDL levels, and that long-term administration of NO-1886 to rats with experimental atherosclerosis provides significant protection against the development of coronary artery lesions. (J. Clin. Invest. 1993. 92:411417.)

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Section: Resultsmentioning

confidence: 99%

The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis.

Tsutsumi¹,

Inoue²,

Shima³

et al. 1993

J. Clin. Invest.

141

103

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“…Triton WR1339 acts on VLDL particles such that the degradation of particles is inhibited, leading to an increase in plasma triglyceride and cholesterol levels (Millar et al ., 2002). In contrast, protamine sulfate acts on LPL directly to inhibit its activity, which in turn enhances plasma triglyceride levels but has no effect on plasma cholesterol level (Tsutsumi et al ., 1993; Kaye & Galton, 1975). Both the Triton WR1339 and protamine sulfate treatment models are known to be suitable for evaluating the effects of drugs on VLDL secretion from the liver.…”

Section: Discussionmentioning

confidence: 99%

YM‐53601, a novel squalene synthase inhibitor, suppresses lipogenic biosynthesis and lipid secretion in rodents

Ugawa¹,

Kakuta²,

Moritani³

et al. 2003

British J Pharmacology

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1 To better understand how it decreases plasma cholesterol and triglyceride levels, we evaluated the effect of (E)-2-[2-fluoro-2-(quinuclidin-3-ylidene)ethoxy]-9H-carbazole monohydrochloride (YM-53601) on lipogenic biosynthesis in the liver and lipid secretion from the liver in rats and hamsters. 2 Single administration of YM-53601 in cholestyramine-treated rats inhibited triglyceride and free fatty acid (FFA) biosynthesis at a similar dose range to that at which it inhibited cholesterol biosynthesis. YM-53601 inhibited both triglyceride and FFA biosynthesis in hamsters treated with cholestyramine. 3 YM-53601 by single oral administration decreased the enhanced plasma triglyceride levels in hamsters induced by an injection of protamine sulfate, which inhibits lipoprotein lipase (LPL) and consequently increases plasma very low-density lipoprotein (VLDL) triglyceride levels. YM-53601 also decreased the enhanced plasma triglyceride and cholesterol levels in hamsters treated with Triton WR1339, which also inhibits the degradation of VLDL. Plasma cholesterol was significantly decreased as soon as 1 h after single administration of YM-53601 in hamsters fed a normal diet. 4 This is the first report that a squalene synthase inhibitor suppresses lipogenic biosynthesis in the liver and cholesterol and triglyceride secretion from the liver in vivo. We therefore suggest that the mechanism by which YM-53601 decreases plasma triglyceride might include these effects. The finding that YM-53601 rapidly decreased plasma cholesterol suggests that this compound may be effective in decreasing plasma cholesterol levels early in the course of treatment of hypercholesterolemia in humans.

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“…Our data demonstrated that the chylomicrons derived from type V patients demonstrate a significant increment in triglyceride/ cholesterol ratio in comparison to those lipoproteins obtained from normal subjects after a fatty meal (Table 1). This phenomenon probably results from a sustained inhibition of hepatic cholesterogenesis by chylomicron remmants (21) in type V patients, whereas in normal subjects chylomicron levels increase only transiently after the fatty meal, with only minimal suppression of cholesterol synthesiS. The increased TRP triglyceride content in type V patients may result from both impaired clearance as well as enhanced triglyceride synthesis resulting from increased local free fatty acids by virtue of hepatic lipase activity.…”

Section: Discussionmentioning

confidence: 98%

“…showed triglyceride/cholesterol ratio which fell between chylomicron and VLDL values ( Table 1; Ref. 2). Patients with type V hyperlipoproteinemia have high plasma levels of both chylomicrons and VLDL, and they have a defect in triglyceride clearance (21) which may result from their abnormal TRP ( Figs. 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

Chylomicron‐like particles in severe hypertriglyceridemia

Aviram

Sechter

Brook

1985

Lipids

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Plasma lipoproteins in a diabetic patient with severe hypertriglyceridemia and turbid, milky plasma were studied and compared with those found in three primary type V hyperlipoproteinemic and in three normal subjects after a fatty meal. All subjects had normal post-heparin lipolytic activity. Lipoprotein electrophoresis of the patient's plasma revealed no chylomicron band, and upon short-time ultracentrifugation the patient's supernatant showed most lipid staining in the pre-beta-lipoprotein region. This supernatant, which in type V hyperlipoproteinemia as well as in normal subjects after a fatty meal, contains a large proportion of apolipoprotein B-48 (of intestinal origin), was found in our patient to contain mostly apolipoprotein B-100 (of liver origin). Upon incubation of normal washed platelets with chylomicrons derived either from type V hyperlipoproteinemic or from normal subjects after a fatty meal, platelet aggregation was decreased, whereas the chylomicron-like particles from the patient increased platelet activity. It is, thus, suggested that the triglyceride-rich, cholesterol-poor lipoproteins are of liver and not of intestinal origin.

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Triglyceride-Production Rates in Patients With Type-Iv Hypertriglyceridæmia

Cited by 14 publications

References 12 publications

The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis.

The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis.

YM‐53601, a novel squalene synthase inhibitor, suppresses lipogenic biosynthesis and lipid secretion in rodents

Chylomicron‐like particles in severe hypertriglyceridemia

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