Lipoprotein responses to fish, coconut and soybean oil diets with and without cholesterol in the Syrian hamster

Thirty-six young male Syrian hamsters were fed with test diets containing coconut oil, soybean oil or fish oil with and without 0.5% cholesterol for 6 weeks. Without dietary cholesterol supplementation, animals on the fish oil diet had significantly lower plasma total triglyceride (TG) and total cholesterol than those on the coconut oil or soybean oil diet. The decrease of TG was seen mainly in the very low density lipoprotein (VLDL) fraction. The degree of decrease in cholesterol was similar in all of the lipoprotein fractions. With 0.5% dietary cholesterol supplementation, there was no significant difference in plasma TG level among the three dietary groups. However, the fish oil group had significantly higher plasma cholesterol than the coconut oil and soybean oil groups. The increase of cholesterol was mainly in the VLDL and low density lipoprotein (LDL) fractions. In contrast to the plasma cholesterol level, the hepatic cholesteryl ester content was significantly lower in the cholesterol-supplemented fish oil group than in the coconut oil and soybean oil counterparts. The cholesterol-supplemented fish oil group showed higher liver microsomal acyl-coenzyme A:cholesterol acyltransferase activity than the other two groups, while there was no significant difference in the excretion of fecal neutral and acidic sterols among the three dietary groups.     

The obese client: myths, facts, assessment, and intervention

The effects of evening primrose oil (EPO) treatment, a source of gamma-linolenic acid, on the proportions of arachidonoyl-containing molecular species (ACMS) in sciatic nerve phosphatidylcholine and phosphatidylethanolamine were determined in conjunction with alterations in nerve conduction velocity. Normal and diabetic rats were either untreated or fed a dietary supplement containing isocalorically equivalent amounts of either EPO or corn oil for the duration of the experiment. After 8 weeks of streptozotocin-induced diabetes, nerve conduction velocity was reduced 16% and this deficit was prevented by either EPO or corn oil treatment. Neither EPO nor corn oil supplementation significantly increased the depressed proportions of ACMS. The level of the linoleoyl-containing molecular species, 16:0/18:2, was elevated in the phospholipids from untreated diabetic rats and was further increased by EPO treatment. These results are consistent with decreased activity of the delta6 desaturase that is required for arachidonic acid synthesis in vivo, but suggests that an accompanying deficit in the subsequent delta5 desaturase-catalyzed reaction may be rate-limiting. These findings indicate that maintenance of normal ACMS levels is not required for prevention of diminished nerve conduction velocity and suggest that other factors influenced by an altered polyunsaturated fatty acid pattern, such as metabolites of linoleic acid or gamma-linolenic acid other than arachidonic acid, the energy state of the nerve or the degree of membrane fluidity may contribute to impaired nerve conduction velocity in diabetic neuropathy.     

Postprandial lipoprotein responses in hypertriglyceridemic subjects with and without cardiovascular disease

Three groups of age- and weight-matched men (aged 40 to 70 years) without diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180 mg/dL and no cardiovascular disease (CVD); HTG-CVD (n = 11), hypertriglyceridemic (HTG) (TG > 240 mg/dL) without CVD; and HTG+CVD (n = 10), HTG (TG > 240 mg/dL) with documented CVD. HTG+CVD subjects had higher fasting and post-oral glucose tolerance test insulin levels than the other two groups, respectively. Very-low-density lipoprotein (VLDL)+chylomicrons (CMs), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL) subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups, except for higher VLDL lipid to apolipoprotein (apo) B ratios (P < .04) in the HTG+CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial responses of the core lipids (TG and cholesterol esters [CE]) in all of the lipoprotein subfractions were similar in the two HTG groups at each time point. However, both controls and HTG-CVD subjects had increases in HDL-M phospholipid (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG+CVD group, on the other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D PL. These changes resulted in significant increases in HDL-M and HDL-D PL to apo A-I ratios in both controls and HTG-CVD subjects between 6 and 12 hours, whereas there was no increase seen in the HTG+CVD group. The HTG-CVD group also had a significantly greater increase in the VLDL+CM PL to apo B ratio (P = .038) at 3 hours than the HTG+CVD group. This diminished amount of surface lipid per VLDL particle may account for the late decrease in the HDL-D PL to apo A-I ratio seen in HTG+CVD patients. There were no other postprandial lipid or apolipoprotein differences between the two HTG groups. We conclude therefore that the major postprandial lipoprotein abnormality in these HTG+CVD patients was a failure to increase the PL content per particle in VLDL+CM, HDL-M, and HDL-D. This abnormality could prevent the usual increase in reverse cholesterol transport seen in postprandial plasma and therefore contribute to their increased incidence of CVD. The greater insulin resistance seen in these patients also appears to contribute significantly to their CVD.     

Preparation of chylomicrons and VLDL with monoacid-rich triacylglycerol and characterization of kinetic parameters in lipoprotein lipase-mediated hydrolysis in chickens

To identify the substrate specificity of lipoprotein lipase (LPL) for triacylglycerol-rich lipoproteins with monoacid-rich triacylglycerols, monoacid-rich lipoproteins were prepared and kinetic parameters of LPL were characterized. Male broiler chickens were fed 8 g/100 g fat diets differing only in the fat source: palm oil (tripalmitin-rich), olive oil (triolein-rich), safflower oil (trilinolein-rich) and linseed oil (trilinolenin-rich). After diets were fed for 3 d, chickens were starved for 2 d and then force-fed emulsions containing one of the monoacid-triacylglycerols: tripalmitin, triolein, trilinolein or trilinolenin. The triacylglycerols in chylomicrons and very low density lipoprotein (VLDL) of chickens force-fed tripalmitin, triolein or trilinolein contained the corresponding acid at more than 70% of total acids. Linolenic acid was incorporated into chylomicrons and VLDL to a lower extent (51.2 and 57.2%, respectively) in chickens force-fed trilinolein. Major apolipoproteins and lipid compositions were not significantly different among all lipoproteins isolated from chickens fed the different fats. Vmax of LPL was significantly higher (P < 0.05) for palmitic acid-rich chylomicrons and VLDL and decreased with increasing chain length and unsaturation of monoacid: 16:0>18:1>18:2>18:3. The electron spin resonance analysis, order parameter (S), decreased with monoacid chain length and unsaturation. In addition, the Vmax of LPL increased linearly (P < 0.01, r = 0. 912) with an increase in the palmitic acid content of the lipoprotein triacylglycerols. These findings suggest that lipoprotein catalysis by LPL is modulated by the palmitic acid content of the lipoprotein triacylglycerol, which affects the fluidity of lipoproteins.     

Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males

The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (-29%), VLDL cholesterol (-40%), LDL cholesterol (-27%), and apo B (-16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (-40%; P = .04) and C-PR (-42%; P = .03). Treatment with lovastain in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed.     

A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM

OBJECTIVE: To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks. RESULTS: The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure. CONCLUSIONS: In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control.     

Replacement of partially hydrogenated soybean oil by palm oil in margarine without unfavorable effects on serum lipoproteins

We have compared the effects of three different margarines, one based on palm oil (PALM-margarine), one based on partially hydrogenated soybean oil (TRANS-margarine) and one with a high content of polyunsaturated fatty acids (PUFA-margarine), on serum lipids in 27 young women. The main purpose of the study was to test if replacement of trans fatty acids in margarine by palmitic acid results in unfavorable effects on serum lipids. The sum of saturated fatty acids (12:0, 14:0, 16:0) was 36.3% of total fatty acids in the PALM-diet, the same as the sum of saturated (12:0, 14:0, 16:0) (12.5%) and trans (23.1%) fatty acids in the TRANS-diet. This sum was 20.7% in the PUFA-diet. The content of oleic acid was 37.9, 35.2, and 38.6%, respectively, in the three diets, whereas linoleic acid amounted to 16, 13.5, and 27.3%, respectively. Total fat provided 30-31% and the test margarines 26% of total energy in all three diets. The subjects consumed each of the diets for 17 d in a Latin-square crossover design. There were no significant differences in total cholesterol, low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB) between the TRANS- and the PALM-diets. High density lipoprotein (HDL)-cholesterol and apoA-1 were significantly higher on the PALM-diet compared to the TRANS-diet whereas the ratio of LDL-cholesterol to HDL-cholesterol was lower, although not significantly (P = 0.077) on the PALM-diet. Total cholesterol, LDL-cholesterol, and apoB were significantly lower on the PUFA-diet compared to the two other diets. HDL-cholesterol was not different on the PALM- and the PUFA-diets but it was significantly lower on the TRANS-diet compared to the PUFA diet. Compared to the PUFA-diet the ratio of LDL- to HDL-cholesterol was higher on both the PALM- and the TRANS-diets whereas apoA-1 was not different. Triglycerides and lipoprotein (a) were not significantly different among the three diets. We concluded that nutritionally, palmitic acid from palm oil may be a reasonable alternative to trans fatty acids from partially hydrogenated soybean oil in margarine if the aim is to avoid trans fatty acids. A palm oil-based margarine is, however, less favorable than one based on a more polyunsaturated vegetable oil.     

Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters

Conjugated linoleic acid is a collective term used to designate a mixture of positional and geometric isomers of linoleic acid in which the double bonds are conjugated. Unlike linoleic acid, there is a paucity of information regarding the effect of dietary conjugated linoleic acid on plasma lipoproteins and aortic atherosclerosis. Therefore, fifty hamsters were divided into five groups of ten and fed 0 (Control), 0.06 (LOW), 0.11 (MEDIUM), and 1.1 (HIGH) en% conjugated linoleic acid or 1.1 en% linoleic acid. Blood samples were taken at 4, 8 and 11 weeks for plasma lipid analyses and for plasma tocopherol assay at sacrifice. Animals fed the conjugated linoleic acid-containing diets collectively had significantly reduced levels of plasma total cholesterol, non-high density lipoprotein cholesterol, (combined very low and low density lipoprotein) and triglycerides with no effect on high density lipoprotein cholesterol, as compared to CONTROLs. Linoleic acid-fed animals relative to CONTROLs also had reduced plasma total cholesterol, non-high density lipoprotein cholesterol and triglycerides, but only the latter was statistically significant. Compared to the CONTROL group, plasma tocopherol/total cholesterol ratios determined from plasma pools for the LOW, MEDIUM and HIGH conjugated linoleic acid and linoleic acid groups were increased by 48%, 48%, 86% and 29%, respectively, suggesting a tocopherol-sparing effect, at least for the conjugated linoleic acid treatment. Morphometric analysis of aortas revealed less early atherosclerosis in the conjugated linoleic acid and linoleic acid-fed hamsters compared to the CONTROL group.     

Free fatty acids in gallbladder bile

Using gas chromatography and high performance liquid chromatography (HILC), we examined free fatty acid and lecithin molecular species in gallbladder biles from patients with cholesterol gallstones. Effect of free fatty acids on cholesterol nucleation in model bile was studied by a sensitive cholesterol crystal growth assay. Compared to bile of controls, biles from patients with gallstones had higher total free fatty acid level, more palmitic acid, more stearic acid, more linoleic acid and arachidonic acid. The lecithin pattern was similar in all. After free fatty acids were added to model bile, palmitic acid, oleic, acid, linoleic acid and arachidonic acid had significant effect of pro-nucleating, free fatty acids on non-protein pro-nucleating factor. These data suggest that variations in quantitation and composition of free fatty acids are importanct in the pathogenesis of cholesterol gallstone formation.     

Epoxidation of C18 unsaturated fatty acids by cytochromes P4502C2 and P4502CAA

The regioselective epoxidation of oleic, linoleic, alpha-linolenic, and gamma-linolenic acid by cytochromes P4502CAA and P4502C2 was characterized. Epoxide metabolites for all fatty acids were resolved by normal phase HPLC and identified by gas chromatography and mass spectrometry. Both isoforms epoxidized the single double bond in oleic acid and both double bonds in linoleic acid. The ratio of the two epoxides produced with linoleic acid (1.6:1 for the 12,13- and 9,10-epoxides) was similar for both enzymes. When alpha-linolenic acid was the substrate, all three epoxides were produced in about equal ratios with both enzymes. In contrast for the omega-6 fatty acid, gamma-linolenic acid, both enzymes produced only the 9,10- and 12,13-epoxides. Furthermore, the ratio of the metabolites produced by each enzyme was significantly different. The ratios of 12,13-epoxide to 9,10-epoxide for gamma-linolenic were 11.0 +/- 0.19 and 5.8 +/- 1.2 for P4502CAA and P4502C2, respectively. These results suggest that there may be subtle differences in the structure of 2C2 and 2CAA and also indicate that P450 may be important in the generation of potentially active epoxide metabolites of unsaturated fatty acids other than arachidonic acid.     

Dietary stearic acid reduces plasma and hepatic cholesterol concentrations without increasing bile acid excretion in cholesterol-fed hamsters

Although there is general agreement that saturated fatty acids elevate plasma cholesterol concentrations, the relative effects of individual fatty acids on cholesterol and bile acid metabolism are less clear. In this study, cholesterol and bile acid responses to diets enriched in different saturated fatty acids were investigated in hamsters. The six diets examined were as follows: 5% fat (g/100 g) enriched in palmitic acid (16:0) with no cholesterol, 5% fat 16:0-enriched, 0.05% cholesterol (wt/wt), and four diets containing 0.05% cholesterol and 15% fat with each diet enriched in lauric (12:0), myristic (14:0), palmitic (16:0), or stearic acid (18:0). Total plasma cholesterol concentration was significantly greater in hamsters fed the 14:0-enriched diet relative to those fed the 18:0-enriched diet (P < 0.05). Both plasma and liver cholesterol concentrations of hamsters fed 18:0 did not differ from those of the group fed no dietary cholesterol. In all instances, differences in total plasma cholesterol were accounted for within the HDL fraction; no significant treatment differences in VLDL or LDL cholesterol were found. Total daily fecal bile acid excretion was higher in hamsters fed the 15% fat 16:0 diet compared with those fed no dietary cholesterol (P < 0.05), but not significantly different from other treatment groups. There was greater deoxycholic acid excretion (P < 0.05) from hamsters fed the 14:0 and 16:0 diets compared with those fed the 18:0-enriched diet. Small intestinal + gallbladder bile acids, an index of pool size, did not differ significantly among the groups. The observed relative hypocholesterolemic effect of stearic acid was not mediated by increased bile acid excretion.     

Regulation of plasma lipoprotein levels by dietary triglycerides enriched with different fatty acids

Saturated vegetable oils (coconut, palm, and palm kernel oil) containing predominantly saturated fatty acids, lauric (12:0) or myristic (14:0 and palmitic (16:0), raise plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in animals and humans, presumably by decreasing LDL receptor activity and/or increasing LDL-C production rate. Although stearic acid (18:0) is chemically a saturated fatty acid, both human and animal studies suggest it is biologically neutral (neither raising nor lowering) blood cholesterol levels. Although earlier studies indicated that medium chain fatty acids (8:0-10:0) were also thought to be neutral, more recent studies in animals and humans suggest otherwise. Unsaturated vegetable oils such as corn, soybean, olive, and canola oil, by virtue of their predominant levels of either linoleic acid (18:2) or oleic acid (18:1), are hypocholesterolemic, probably as a result of their ability to upregulate LDL receptor activity and/or decrease LDL-C production rate. Whether trans fatty acids such as trans oleate (t18:1), in hydrogenated products such as margarine, are hypercholesterolemic remains controversial. Studies in humans suggest that their cholesterol-raising potential falls between the native nonhydrogenated vegetable oil and the more saturated dairy products such as butter. Assessment of the magnitude of the cholesterolemic response of trans 18:1 is difficult because in most diet studies its addition is often at the expense of cholesterol-lowering unsaturated fatty acids, making an independent evaluation almost impossible.     

Fatty acid composition of plasma phosphatidylcholine and levels of lipids and lipoproteins in hyperlipoproteinemia. II. Relation with B lipoproteins

BACKGROUND: Epidemiological trials provided evidence that the cholesterol concentration in lipoproteins B, i.e. VDL, IDL and LDL, correlate significantly with the incidence of ischaemic heart disease (IHD). The objective of the present study was to assess how the fatty acid composition in plasma phosphatidyl choline affects the total and LDL cholesterol, triglyceride and apolipoprotein B concentrations in subjects with primary hyperlipoproteinaemia and dyslipidaemia. METHODS AND RESULTS: In a group of 142 subjects with primary hyperlipoproteinaemia and dyslipidaemia the concentrations of plasma lipids, lipoproteins apolipoproteins and fatty acids in plasma phosphatidyl choline (PC) were assessed. The authors provided evidence by discriminant analysis where the dependent variables were the lower quintiles (Q1 + Q2) and the upper quintiles (Q4 + Q5) of concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B and the independent variables were FA concentrations in plasma PC, that the total cholesterol concentration was inversely associated with the concentration of docosahexaenic acid (22:6n-3). The concentration of LDL-cholesterol correlated inversely with the concentration of palmitoleic acid (16:1n-7). Triglyceridaemia was inversely associated with the linoleic acid concentration (18:2n-6). The concentration of apolipoprotein B correlated positively with myristic acid (14:0) and negatively with concentrations of oleic acid (18:1n-9) and linoleic acid (18:2n-6). CONCLUSIONS: The submitted results indicate that the fatty acid concentrations of PC in plasma are significantly and markedly correlated with concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B. It is possible that atherogenic lipoproteins may be favourably influenced not only by the amount of fat but also by a suitable fatty acid composition.     

Binocular processes in vernier acuity

The contribution of synthesis and dietary sequestration to the high arachidonate content of the lone star tick, Amblyomma americanum, salivary glands was investigated by assessing the salivary metabolites of various radiolabeled fatty acid substrates administered to partially fed females. A portion of each of the fatty acids studied was incorporated into the fatty acid moiety of the phospholipid fraction. [14C]acetate was metabolized only into myristic, palmitic, palmitoleic, steric, and oleic acids. [3H]oleic acid, [14C]linoleic acid, [14C]gamma-linolenic acid and [14C]eicosatrienoic acids were incorporated into salivary gland phospholipids but underwent little change including elongation and/or desaturation to arachidonate. Ingested [3H]arachidonic acid was readily taken up by the salivary gland and distributed among the lipid classes in a pattern markedly different from that of the other fatty acids tested. We conclude that ticks are unable to synthesize arachidonic acid for incorporation into the salivary glands, but rather sequester it from the host bloodmeal.     

Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor protein and mRNA abundance in young pigs

The present study was conducted to determine the effects of dietary fatty acids on hepatic LDL receptor (LDLr) protein abundance and mRNA levels. Sixty pigs were randomized into 10 groups and fed corn-soybean meal diets containing three cholesterol levels (0.25%, 0.5%, and 1.0%, w/w) with no added fat, or fats rich (30% of calories) in palmitic acid or linoleic acid. A control group was fed the base diet with no added fat. After 30 days, plasma LDL-cholesterol (LDL-C) levels increased as the dietary cholesterol increased (P < 0.05); however, there was no significant effect of either fatty acid. Dietary fatty acids, however, had distinctly different effects on hepatic LDLr protein (analyzed by ELISA) and mRNA (analyzed by Northern blot) abundance. When pigs consumed diets containing 0.25% cholesterol, linoleic acid increased hepatic LDLr protein 40% whereas palmitic acid reduced it 40% (P < 0.05). These changes in LDLr protein abundance were accompanied by parallel changes in hepatic LDLr mRNA; linoleic acid increased LDLr mRNA 2-fold (P < 0.01), whereas palmitic acid decreased it 60% (P < 0.01). The differential effects of fatty acids on LDLr expression were only observed at 0.25% cholesterol, suggesting that higher intakes of cholesterol have a dominant and repressive effect on regulation of LDLr expression. Cholesterol intake increased hepatic total cholesterol levels (P < 0.01) while dietary fatty acids had no effect on hepatic sterols. In summary, our results indicate that dietary linoleic acid and palmitic acid have markedly different effects on hepatic LDLr protein abundance that are mediated by differential effects on LDLr mRNA and protein levels. Further studies are needed to fully elucidate the molecular mechanisms by which fatty acids regulate LDLr mRNA and protein levels.     

Hyperinsulinemia and insulin resistance are associated with multiple abnormalities of lipoprotein subclasses in glucose-tolerant relatives of NIDDM patients. Botnia Study Group

We studied the subclasses of plasma lipoproteins in normolipidemic, glucose-tolerant male relatives of noninsulin dependent diabetic patients (NIDDM), who represented either the lowest (n = 14) or the highest (n = 18) quintiles of fasting plasma insulin. The higher plasma triglyceride level in the high insulin group (1.61 mmol/l vs. 0.87 mmol/l, P < 0.001) was due to multiple differences in triglyceride-rich lipoproteins. The concentrations of larger VLDL1, smaller VLDL2 particles, and IDL particles were 3.8-fold, 2.5-fold, and 1.5-fold higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In addition, hyperinsulinemic subjects had VLDL1, VLDL2, and IDL particles enriched in lipids and poor in protein. The lower plasma HDL cholesterol level in the high insulin group (1.20 mmol/l vs. 1.44 mmol/l, P < 0.01) compared to the low insulin group was a consequence of a 27% reduction of HDL2a concentration (P < 0.05) and a significantly reduced percentage of cholesterol in HDL3a, HDL3b, and HDL3c subclasses. On the other hand, the percentages of triglycerides in HDL2b, HDL2a, HDL3a, and HDL3b subclasses were 76%, 79%, 61%, and 50% higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In the combined group, the concentration of VLDL1 and VLDL2 correlated positively with the concentrations of LDL2 and LDL3 and negatively with HDL2b and HDL2a subclasses (P < 0.05 or less). In conclusion, normolipidemic, glucose-tolerant but hyperinsulinemic relatives of NIDDM patients have qualitatively similar lipoprotein abnormalities as NIDDM patients. These abnormalities are not observed in insulin-sensitive relatives, suggesting that they develop in concert with insulin resistance.     

Effects of animal and soy fats and proteins in the diet on fatty acid concentrations in the serum and skin of dogs

Growing dogs were fed diets containing soy oil or poultry fat as the main fat source and soybean meal or meat meal as the main protein source to examine the effects of types of dietary fat and protein on fatty acid concentrations in serum and skin and on serum cholesterol concentrations. Dogs fed diets containing soy oil had higher serum linoleic acid concentrations and lower serum oleic acid, arachidonic acid, and cholesterol concentrations than dogs fed diets containing poultry fat. The type of dietary protein had marginal effects on fatty acid concentrations and did not affect serum cholesterol. Similar differences were found in cutaneous fatty acid concentrations, with soy oil-fed dogs having significantly (P < 0.05) higher linoleic acid and lower oleic acid concentrations in their skin than had poultry fat-fed dogs. This study suggested that dietary fat source influences serum and cutaneous fatty acid concentrations and serum cholesterol concentrations in dogs, irrespective of dietary protein source.     

Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Synaptic proteins of the temporal associative area of the neocortex of cats (field Ep) with normal and reduced cognitive capacities

Genetically hypercholesterolaemic RICO rats (male, 6 weeks old) were randomly distributed into 6 experimental groups. The zero-time basal group A was sacrificed at the start of the experiment while the other groups were fed for 6 weeks and then sacrificed. Group B was fed a stock diet. Control group C was fed a high-sucrose (45%) diet with 0.5% added cholesterol. In the diet of group D, only the magnesium (Mg) content was reduced from the level of group C (883 ppm) to 200 ppm. The diet of group E was the same as that of group D with the addition of 12 ppm of fluoride (F) and the diet of group G was the same as that of group E, but with its Mg content elevated from 200 ppm to 300 ppm. Analysis of aortic blood samples, taken before sacrifice, indicated significant increases in total serum cholesterol (p < 0.01), very low density lipoprotein (VLDL) (p < 0.001) and low density lipoprotein (LDL), (p < 0.001) cholesterol, and a trend to lower high density lipoprotein (HDL) cholesterol in group C, as compared to group B. Significantly lower total (p < 0.05), VLDL (p < 0.01) and LDL (p < 0.01) triglycerides were observed in group C when compared to group B. The LDL phospholipids were significantly higher in group C (p < 0.001) than in group B. When cholesterol levels in groups D, E and G were compared with group C, the VLDL cholesterol in group E and the LDL cholesterol in group G were slightly but significantly (p < 0.05) reduced, while total cholesterol and the other subfractions were unaltered. The LDL triglycerides of groups E and G were significantly smaller still than the already small fraction in group C. The VLDL triglyceride in group E was significantly lower than that of group C (35% reduction, p < 0.001), D and G (p < 0.05). Phospholipids were slightly but significantly reduced in the VLDL fraction of group E and in the LDL fraction of group G (p < 0.05 and 0.01, respectively), as compared to those of group C.     

Clinical and genetic analysis of a pedigree of a thirty-six-year-old familial Alzheimer''s disease patient

Distribution of apolipoprotein(apo) E4 and E3 in lipoproteins of serum with apoE4/E3 phenotype was analyzed. ApoE was eluted in two major peaks by gel chromatography; peak 1 and 2 corresponding to very- and intermediate-low density lipoprotein (VLDL + IDL) and high density lipoprotein2 (HDL2), respectively. ApoE in peak 1 (VLDL + IDL) consisted of monomers of 34 kDa, complexes with a high molecular weight (apoEs) of 100 kDa and with a small amount of apoE-AII complexes weighing 43 kDa. In contrast, apoE in peak 2 (HDL2) was composed mainly of apoE-AII complexes and apoEs complexes, and a small amount of monomers. Both apoE3 and E4 isoforms were detected in these peaks; E4 was more predominant in peak 1 while E3 was more predominant in peak 2. These findings suggest that different distributions of apoE3 and E4 in lipoprotein particles.