Rapid induction of essential fatty acid deficiency by intragastric infusion of triolein-supplemented total parenteral nutrition solutions: evidence of increased hepatic cholesterol esterification in the rat

Rats were fed linoleic acid from a safflower oil emulsion or triolein-supplemented total parenteral nutrition solutions by continuous intragastric infusion for 7 and 14 d. Biochemical signs of essential fatty acid deficiency (EFAD) developed in rats supplemented with triolein compared with those receiving linoleic acid, and the relationship between hepatic cholesterol esterification and the distribution of free cholesterol in plasma lipoproteins was investigated in the EFAD and control animals. Results indicate that hepatic triglyceride (TG) and cholesterol ester content are greater and plasma levels of TG and cholesterol are lower in triolein-supplemented groups. Hepatic accumulation of cholesterol esters is associated with an increase in hepatic acyl-CoA:cholesterol acyltransferase activity and also with plasma very low density lipoprotein (VLDL) and high-density lipoprotein (HDL), which contain a greater proportion of cholesterol esters. These data suggest that EFAD can be rapidly induced with continuous intragastric feeding and that hepatic accumulation of cholesterol esters and enrichment of VLDL and HDL with cholesterol esters are early indicators of EFAD in the rat.     

Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats

We investigated the relative effects of different dietary saturated fats on the size distribution, apolipoprotein (apo) and chemical composition of HDL in fasted rats. Male Sprague-Dawley rats (174 +/- 2 g) were fed diets containing 0.035% cholesterol and 16% fat (wt/wt) from corn oil (CO diet) or from 2% CO plus 14% butterfat (BF diet), beef tallow (BT diet), palm oil (PO diet) or coconut oil (CN diet) for 6 wk. Apparent lipid digestibility was significantly lower with the PO and BT diets vs. the CO, BF and CN diets. Plasma total cholesterol levels were significantly higher in rats fed the PO and BT diets than in rats fed the BF and CN diets but were not different among the PO-, BT- and CO-fed groups. Nondenaturing gradient gel electrophoresis immunoblot analysis indicated that HDL apo A-I and E resided on particles with significantly smaller modal diameters in rats fed all saturated fats compared with those fed the CO diet. Chemical analyses indicated that HDL generally contained proportionately less protein and more triglyceride, free cholesterol and apo E with saturated fat feeding than with CO diet feeding. Significantly higher plasma and VLDL triglyceride levels were noted with ingestion of the BT, PO or CN diet than with the CO diet. Butterfat feeding resulted in lower plasma triglycerides and HDL-esterified cholesterol than did feeding the other saturated fats. Very low density lipoprotein triglyceride concentrations were inversely correlated with HDL modal diameter of apo E containing lipoproteins (P less than 0.005). These data provide further evidence of the interrelationship of triglyceride and HDL metabolism and suggest that mechanisms independent of cholesterol ester transfer protein may mediate this response in rats.     

Cholesterol and apolipoprotein distribution in plasma high-density-lipoprotein subclasses from zinc-deficient rats

Effect of zinc deficiency on the composition of plasma high-density-lipoprotein (HDL) subclasses was investigated in adult male rats (ZD) fed a diet containing 2.8 micrograms of Zn/g as compared with pair-fed (PF) and ad libitum-fed (CT) controls given 30.8 micrograms of Zn/g. Three HDL subclasses were isolated by heparin-affinity chromatography: HDL containing no apo E (HDL-E0), HDL with a moderate amount of apo E (HDL-E1), and HDL highly enriched in apo E (HDL-E2). The plasma levels of total HDL cholesterol and protein were markedly decreased in ZD. The decreases were due primarily to a significant decline in circulating HDL-E0 particles. The percent content of free cholesterol in HDL-E2 was increased in ZD compared with PF and CT. Zn deficiency decreased the plasma concentrations of apo A-I and apo C of HDL-E0 and total apo E associated with HDL-E1 and HDL-E2. The mechanisms for such changes await further investigation.     

Magnesium deficiency affects plasma lipoprotein composition in rats

Weanling rats were pair-fed for 8 d with control and Mg-deficient diets containing 960 and 30 mg of Mg/kg, respectively. The marked reduction in plasma Mg levels indicated that the rats fed the Mg-deficient diet were indeed deficient. In the Mg-deficient rats the percent composition of triglycerides in VLDL, LDL and HDL was elevated and that of protein was reduced. Although the proportion of cholesterol was reduced in LDL and HDL, that of phospholipid was decreased only in HDL. Magnesium deficiency induced a decrease in the percent composition of apolipoprotein (apo) E and a relative increase in the apo C for VLDL. In HDL from Mg-deficient rats, the proportion of apo AI was higher than normal, apo AIV was lower than normal and apo E was virtually absent. The percent composition of oleic and linoleic acids was increased but that of stearic and arachidonic acids was depressed in both VLDL and HDL derived from Mg-deficient rats compared with pair-fed controls. Whether these alterations in lipoprotein profile contribute to hyperlipoproteinemia or are the results of the metabolic changes that produce hyperlipoproteinemia remain to be determined.     

Different effects of zinc and copper deficiency on composition of plasma high density lipoproteins in rats

Male Sprague-Dawley rats (six per group) were fed an egg white-based diet containing 0 or 5 micrograms/g Cu with 1, 10, 100 or 1000 micrograms/g Zn. After 6 wk of feeding, the rats were killed, and the tissues were processed for trace element, lipid and lipoprotein analysis. Copper deficiency was associated with a higher concentration of plasma free cholesterol, high density lipoprotein (HDL) cholesterol and HDL apolipoproteins. Plasma total cholesterol was not significantly affected. No significant differences were noted in HDL lipid composition. However, HDL apo E and apo A-I concentrations were higher with copper deficiency. Lecithin:cholesterol acyltransferase (LCAT) was not affected in a consistent manner by copper status. Varying the amount of zinc in the diet did not produce significant changes in plasma total cholesterol, plasma free cholesterol, HDL cholesterol, or HDL apolipoprotein concentrations. However, HDL from zinc-deficient rats were enriched in free cholesterol and depleted in triglycerides. Furthermore, the concentration of HDL apo C increased as the level of dietary zinc increased.     

Manganese, iron and lipid interactions in rats

The interactive effects of manganese, iron and lipid on mineral status, manganese-dependent superoxide dismutase (MnSOD) activity and lipoprotein composition were investigated by feeding weanling rats two levels of manganese (0.4 or 56 micrograms Mn/g diet), two levels of iron (29 or 109 micrograms Fe/g diet) and either 12% high-linoleic acid safflower oil or 12% high-oleic acid safflower oil for 8 wk. Rats fed the manganese-deficient diets had decreased heart MnSOD activity; depressed tibia and kidney manganese concentrations; lowered plasma and high density lipoprotein (HDL) cholesterol, HDL protein and HDL apo E concentrations; and elevated HDL protein/cholesterol ratios. Ingestion of supplemental iron slightly decreased heart MnSOD activity and tibia and kidney manganese concentrations but had no effect on hematocrits or on plasma and HDL cholesterol levels. Rats fed the linoleic acid-rich rather than the oleic acid-rich oil had increased heart MnSOD activity but had unchanged plasma and HDL cholesterol levels. The decrease in plasma and HDL cholesterol levels with manganese deficiency appeared not to be a result of increased lipid peroxidation but may have resulted from decreased cholesterol synthesis and/or secretion.     

Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women

BACKGROUND: Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations. However, the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear. OBJECTIVE: The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol, apolipoprotein (apo) A-I, apo B, lipoprotein(a), and total, LDL, and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. DESIGN: In a randomized crossover trial, fasting plasma samples were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein (ISP) consumption providing an average of 7.1 +/- 1.1 (control), 65 +/- 11 (low isoflavone), or 132 +/- 22 (high isoflavone) mg isoflavones/d. RESULTS: Compared with values measured during the control diet, the plasma LDL cholesterol concentration was 6.5% lower (P < 0.02) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the low- and high-isoflavone diets, respectively (P < 0.02). Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol, triacylglycerol, apo A-I, apo B, or lipoprotein(a) or the LDL peak particle diameter. CONCLUSIONS: Consumption of isoflavones as a constituent of ISP resulted in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Although the effects were small, it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies.     

Relative effects of dietary oleic- and linoleic-rich oils on plasma lipoprotein composition in rats

Plasma lipoprotein composition and hepatic lipid content were investigated in male Sprague-Dawley rats (104 +/- 2 g) fed diets containing 12% olive oil [OO, 70% 18:1(n-9)], 12% high oleic safflower oil [SO, 70% 18:(ln-9)] or 12% high linoleic safflower oil [SL, 73% 18:2(n-6)] for periods of up to 10 wk. Fasting plasma triglycerides were significantly higher after feeding oleic-rich diets than after feeding SL for 3, 5 and 6 wk. At 6 wk VLDL triglycerides were two- to threefold higher in rats fed OO or SO than in those fed SL, but by 10 wk both plasma and VLDL triglycerides were similar. A greater proportion of HDL2 (diameter 8.0-12.1 nm), a lower proportion of HDL1 (diameter 12.2-17.0 nm) and lower HDL apo E content occurred in rats fed OO and SO than in those fed SL at both 6 and 10 wk. LDL and HDL protein and cholesterol concentrations were not different with feeding SO or SL. After 10 wk of feeding the experimental diets, rats fed OO had significantly lower HDL protein, cholesterol and apo E concentrations and significantly higher hepatic triglyceride content compared to rats fed SO or SL, P less than 0.05. These data suggest that HDL and hepatic lipid content are determined by some property of the dietary oil other than its oleic acid content.     

Composition of high density lipoproteins in rats fed various dietary fibers

Several studies have suggested that dietary fibers, especially water-soluble sources, are effective agents for lowering plasma cholesterol. This study was undertaken to determine the effect of various fibers on the composition of apoproteins in high density lipoproteins. Rats were fed experimental diets that contained either 20% wheat bran, oat bran or cellulose or 5% pectin or guar gum for 4 weeks. Final body weight was similar among groups. HDL cholesterol and total apoprotein concentrations were not significantly altered by diet. The percentage of apo A-I was significantly elevated and apo E and the apo C's were significantly lower in the guar gum group relative to the wheat bran group. Lecithin cholesterol acyl transferase activity and the C-II-to-C-III ratio were highest in the guar gum group. Differences in the absorption and subsequent metabolism of lipid could account for differences in HDL composition.     

Altered high density lipoprotein composition in manganese-deficient Sprague-Dawley and Wistar rats

The objective of this experiment was to determine whether changes in liver cholesterol content, plasma lipids and lipoprotein composition result from dietary manganese (Mn) deficiency in the Sprague-Dawley (SD) and the Wistar (W) rat. Weanling rats of both strains were fed Mn-deficient (1 ppm Mn) or Mn-adequate (45 ppm Mn) diets for 10 wk. After the 10-wk period rats were killed and plasma, liver, kidney and heart were collected. Liver, kidney and heart Mn concentrations were significantly lower in the rats fed the Mn-deficient diet than in controls. Plasma high density lipoprotein (HDL) (density 1.050-1.1963) was isolated by sequential ultracentrifugation. Plasma cholesterol levels were similar for all groups. HDL protein, cholesterol and apo E levels were significantly reduced with Mn deficiency. A shift to a smaller HDL particle was associated with Mn deficiency, based on gradient gel electrophoresis. The shift in size was more pronounced in the SD strain. Liver concentrations of total and free cholesterol were lower with Mn deficiency but more noticeably in the SD group. The results of our study suggest a role for Mn in HDL metabolism in vivo in both SD and W rats with a trend toward a greater effect in the SD strain.     

Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats

BACKGROUND: Plasma apolipoprotein (apo) E, a sialoprotein, plays an important role in reverse cholesterol transport. Previously, we showed that chronic alcohol consumption impairs glycosylation of apo E in rat liver. Peritoneal macrophages are another significant apo E synthesis site. OBJECTIVE: The main purpose of this study was to determine the effects of chronic alcohol feeding of rats on the synthesis, sialylation, and sialic acid content of macrophage apo E and its ability to bind to the HDL(3) molecule in vitro. DESIGN: Rats were fed an alcoholic diet or an isoenergetic control diet for 8 wk, after which peritoneal macrophages isolated from them were cultured and analyzed for apo E metabolism. RESULTS: Macrophages from alcohol-fed rats accumulated 33.3% more (P < 0.05) cholesterol than did those from control rats when incubated with acetylated LDL. These macrophages showed a 51-57% lower relative sialylation rate of apo E (P < 0.001) but no significant difference in relative protein synthetic rate. The sialic acid content of the intracellular and secreted forms of apo E was reduced by 41.8% (P < 0.001) and 50.3% (P < 0.001), respectively, with chronic alcohol treatment. Secretion of newly synthesized apo E was impaired by 53.7% (P < 0.001) and 26. 1% (P < 0.001) in the absence and presence of HDL in the medium, respectively. Macrophages of alcohol-treated rats secreted apo E with 47.6-67.2% lower (P < 0.001) HDL(3) binding ability; binding ability was restored completely by resialylation of the desialylated apo E. CONCLUSION: In rats, an alcohol-mediated decrease in sialylation rate resulting in loss of sialic acid residues in apo E impairs the ability of apo E to bind to HDL and consequently in defective reverse cholesterol transport.     

Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity

BACKGROUND: Disturbed HDL metabolism in insulin-resistant, obese subjects may account for an increased risk of cardiovascular disease. Fish oils and atorvastatin increase plasma HDL cholesterol, but the underlying mechanisms responsible for this change are not fully understood. OBJECTIVE: We studied the independent and combined effects of fish oils and atorvastatin on the metabolism of HDL apolipoprotein A-I (apo A-I) and HDL apo A-II in obese men. DESIGN: We conducted a 6-wk randomized, placebo-controlled, 2 x 2 factorial intervention study of the effects of fish oils (4 g/d) and atorvastatin (40 mg/d) on the kinetics of HDL apo A-I and HDL apo A-II in 48 obese men with dyslipidemia with intravenous administration of [d3]-leucine. Isotopic enrichments of apo A-I and apo A-II were measured with gas chromatography-mass spectrometry with kinetic parameters derived from a multicompartmental model (SAAM II). RESULTS: Fish oils and atorvastatin significantly decreased plasma triacylglycerols and increased HDL cholesterol and HDL2 cholesterol (P < 0.05 for main effects). A significant (P < 0.02) main effect of fish oils was observed in decreasing the fractional catabolic rate of HDL apo A-I and HDL apo A-II. This was coupled with a significant decrease in the corresponding production rates, accounting for a lack of treatment effect on plasma concentrations of apo A-I and apo A-II. Atorvastatin did not significantly alter the concentrations or kinetic parameters of HDL apo A-I and HDL apo A-II. None of the treatments altered insulin resistance. CONCLUSIONS: Fish oils, but not atorvastatin, influence HDL metabolism chiefly by decreasing both the catabolism and production of HDL apo A-I and HDL apo A-II in insulin-resistant obese men. Addition of atorvastatin to treatment with fish oils had no additional effect on HDL kinetics compared with fish oils alone.     

Soluble oat fiber tends to normalize lipoprotein composition in cholesterol-fed rats

The effect of oat fiber on VLDL, LDL and HDL composition was investigated by feeding male Sprague-Dawley rats diets containing 1.0% cholesterol and 0.2% cholic acid, and 6% dietary fiber from oat bran, high-fiber oat flour or a processed oat product for 20 d. Compared to cholesterol-fed cellulose controls, all oat fibers altered the response to cholesterol feeding as indicated by 25-45% lower total lipoprotein cholesterol, 40-60% lower VLDL + LDL cholesterol, and 25-40% higher HDL cholesterol contents, P less than 0.01. The effect of the oat fibers on VLDL composition was especially pronounced as demonstrated by 30-65% lower VLDL protein, VLDL apo E and plasma apo B concentrations. The processed oat product which contained 40% more soluble fiber than oat bran or oat flour normalized the lipoprotein profile associated with ingestion of the atherogenic diet significantly more than oat bran or oat flour. Concentration of total lipoprotein cholesterol and distribution of apo E among the VLDL and LDL fractions in the processed oat product group were similar to controls not fed cholesterol. These data indicate that ingestion of oat fiber tends to normalize the lipoprotein profile induced by feeding an atherogenic diet in the rat, and that the hypocholesterolemic effect of oat fiber is associated with its soluble fiber content.     

Roles of omega 3 fatty acids and chronic ethanol in the regulation of plasma and liver lipids and plasma apoproteins A1 and E in rats

Relative effects of feeding ethanol and/or omega 3 fatty acid-rich fish oil for 6 wk on body lipids and lipoproteins were investigated. Ethanol increased plasma cholesterol (P less than 0.06) and triglycerides (P less than 0.0005), whereas fish oil decreased plasma cholesterol (P less than 0.005) and triglycerides (P less than 0.02). Liver cholesterol and triglycerides were increased by ethanol (P less than 0.0001) while fish oil decreased liver cholesterol (P less than 0.01) but not triglycerides. Based on Scheffé contrasts (P less than 0.05), fish oil blocked the increases in liver cholesterol and triglycerides caused by ethanol. Substitution of normal dietary fat with omega 3 fatty acid-rich fat in ethanol-fed animals lowered plasma cholesterol by 29% (P less than 0.001) and triglycerides by 30% (P less than 0.05) within 2 wk. Plasma apo A1 was increased by ethanol (P less than 0.001) and decreased by fish oil (P less than 0.002). Plasma total apo E was unaffected by either ethanol or fish oil. However, HDL apo E was decreased by ethanol (P less than 0.04) and increased by fish oil (P less than 0.02). Scheffé contrasts (P less than 0.05) also showed that plasma apo A was increased by ethanol regardless of whether the animals were consuming regular fat (1.72-fold) or fish oil fat (1.49-fold). Thus, omega 3 fatty acids can not only prevent but also reverse many of the lipid and lipoprotein abnormalities caused by alcohol abuse in the rat.     

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effect of taurine on serum lipoprotein metabolism in hypercholesterolemic rats

It is well known that taurine, a final metabolite of sulfur-containing amino acids, plays an important role in bile acid metabolism and that it also has a moderately hypotensive effect. Moreover, it has recently been revealed that taurine shows a hypocholesterolemic effect in animals with experimentally induced hypercholesterolemia. However, the hypocholesterolemic mechanism remains unresolved. Stroke-prone spontaneously hypertensive rats (SHRSP) easily develop hypercholesterolemia when fed a high-fat and high-cholesterol diet (HFC diet). In our previous paper, we reported changes in the concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and Kyo: Wistar rats (WKY) induced by HFC feeding. In this paper, to elucidate the mechanism of the hypocholesterolemic effect of taurine, we investigated the effects of taurine on concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and WKY induced by HFC feeding. The results obtained were as follows: 1) The hypocholesterolemic effect of taurine in hypercholesterolemic SHRSP was remarkable in comparison with that in hypercholesterolemic WKY. 2) The hypocholesterolemic effect of taurine was mainly due to a marked suppression of extreme elevations of cholesterol contents in the VLDL and IDL fractions of both strains. This was associated with a decrease in the elevated contents of apo B and apo E which are major components of VLDL and IDL. This suppressive effect was more obvious in SHRSP than in WKY, which explains the greater hypocholesterolemic effect of taurine in SHRSP. It could be that, as a result of taurine administration, the catabolism of cholesterol to bile acid in the liver is accelerated, followed by a decrease of the hepatic cholesterol pool, resulting in a suppression of the synthesis and/or secretion of VLDL (beta-VLDL) in the liver. 3) The hypocholesterolemic effect of taurine was also observed in the LDL fractions of both strains, but the effect was not as strong as that observed in the VLDL and IDL fractions. This effect might be attributable to suppression of the synthesis and/or secretion of LDL in the liver and a decrease in the elevated content of apo E HDL (HDLc) which spans two density fractions (the LDL and HDL fractions). 4) In HDL fractions of both strains, the decreased content of apo E HDL (HDL1 and HDLc) was even lower, whereas the decreased apo A-I content in the HDL fraction of SHRSP was significantly restored and the cholesterol level was slightly elevated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of plasma lipoproteins and sex hormones to the consumption of lean fish incorporated in a prudent-type diet in normolipidemic men

OBJECTIVE: The effects of lean fish on plasma lipoproteins, postheparin plasma lipolytic activities and sex hormones were examined in 11 normolipidemic male subjects. METHODS: This study was a randomized crossover trial of two isoenergetic prudent-type diets, lean fish diet and beef, pork, veal, eggs and milk (nonfish) diet. Experimental diets provided approximately 11800 kJ--18% as proteins, 50% as carbohydrates, 32% as lipids [ratio of polyunsaturated to saturated fatty acids (P:S) of 1:1 compared with 0.5:1 in preexperimental diet], and 260 mg cholesterol/day. RESULTS: Compared with the nonfish diet, the lean fish diet induced higher plasma total and LDL apolipoprotein (apo) B and apo B:apo A-1 ratio, indicating that the substitution of lean fish for beef, veal, pork, eggs and milk provides little benefits with regard to plasma apo B concentrations in a low-fat high P:S diet. Moreover, triglycerides:apo B and cholesterol:apo B ratios of VLDL were lower following the lean fish diet than the nonfish diet, suggesting the presence of smaller very low-density lipoprotein (VLDL) particles following the consumption of lean fish. Higher plasma concentrations of sex hormone-binding globulin (SHBG), HDL2 cholesterol and HDL2:HDL3 cholesterol ratio were found with the lean fish diet compared with the nonfish diet. Negative correlations between plasma postheparin lipoprotein lipase (LPL) activity and VLDL triglycerides (n = 11, r = -0.53, p = 0.02), and between plasma postheparin LPL activity and VLDL triglycerides:apo B ratio (n = 11, r = -0.64, p = 0.02) were also observed following the lean fish diet. CONCLUSION: These results suggest that the effects of substituting lean fish for beef, veal, pork, eggs and milk on plasma lipoproteins may be partly associated with variations in plasma sex hormone status and plasma LPL activity in normolipidemic men.     

Cholesterol metabolism in rat is affected by protocatechuic acid

The effects of protocatechuic acid on serum cholesterol and gene expression related to cholesterol metabolism in rats were investigated. Rats were fed a cholesterol-free diet with or without 5 g protocatechuic acid/kg diet for 4 wk. There were no significant differences in body weight and food intake among groups through the experimental period. The liver weight in the protocatechuic acid group was significantly lower than that in the control group. The serum total cholesterol, high-density lipoprotein (HDL)-cholesterol and very low-density lipoprotein (VLDL)+intermediate density lipoprotein (IDL)+low-density lipoprotein (LDL)-cholesterol concentrations in the protocatechuic acid group were significantly lower than those in the control group through the feeding period. The hepatic cholesterol concentration in the protocatechuic acid group was significantly higher than in the control group at the end of the 4-wk feeding period. The relative hepatic LDL receptor, apo B, apo E, lecithin-cholesterol acyltransferase (LCAT) and hepatic triglyceride lipase (HTGL) mRNA levels in the protocatechuic acid group were significantly higher than those in the control group. The results of this study suggest the possibility that the increase in the hepatic LDL receptor, apo E, LCAT and HTGL guessed by these mRNAs increase in the protocatechuic acid group lowers the serum total cholesterol level.     

Effect of deficiency of vitamins C and/or E on lipoprotein metabolism in osteogenic disorder Shionogi rat,a strain unable to synthesize ascorbic acid

The effects of vitamin C and/or E deficiency on lipoprotein metabolism were investigated in the inherently scorbutic Osteogenic Disorder Shionogi (ODS) rat. In the vitamin C-deficient (C-def) group, marked increases in plasma VLDL and LDL cholesterol were observed (by comparison with the vitamins C- and E-sufficient control group). In rats kept deficient in both vitamin C and vitamin E (C,E-def), LDL cholesterol was significantly higher than in the C-def group even though the levels of VLDL and HDL cholesterol were similar between the two groups. TBARS values for the LDL fraction in the C-def group were of the same magnitude as in the E-def group, and these values were significantly higher than those obtained for the control group. In the C,E-def group, the values were even higher than in the E-def and C-def groups. The nondenatured PAGE of the LDL fraction indicated the appearance of HDLc in the C-def and C,E-def groups. The SDS-PAGE of the LDL fraction showed increased apo B-48 in the C-def and C,E-def groups and increased apo E in the C,E-def group. Decreased plasma LCAT activity in the E-def, C-def, and C,E-def groups indicated an alteration in HDL metabolism as a result of oxidation. These results suggest that lipid peroxidation and some distinct features of lipoprotein metabolism resulting from vitamin C deficiency become more significant when vitamin E is also deficient along with vitamin C deficiency.     

Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children.

We have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8-11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low-density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high-density lipoprotein-apo E (HDL-E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL-cholesterol, and apo B and to raise levels of HDL-E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL-cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with the PvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL-cholesterol, apo B, and HDL-E levels, respectively, in boys, while in girls only the effect on HDL-E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effects are gender specific.     

Dietary fatty acids and cholesterol differentially modulate HDL cholesterol metabolism in Golden-Syrian hamsters

Dietary fatty acids alter HDL cholesterol concentrations, presumably through mechanisms related to reverse cholesterol transport. The effect of dietary fats (coconut oil, butter, traditional stick margarine, soybean oil, canola oil) differing in fatty acid profile on this antiatherogenic process was assessed with respect to plasma lipids; exogenous and endogenous lecithin-cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), phospholipid transfer protein (PLTP) activities; and LCAT, apolipoprotein (apo) A-I and scavenger receptor B class-1 (SR-B1) mRNA abundance. Golden-Syrian hamsters were fed a nonpurified (6.25 g/100 g fat) diet containing an additional 10 g/100 g experimental fat and 0.1 g/100 g cholesterol for 6 wk. Canola and soybean oils significantly lowered serum HDL cholesterol concentrations relative to butter. Canola oil, relative to butter, resulted in higher exogenous LCAT activity, and both soybean and canola oils significantly increased hepatic apo A-I and SR-B1 mRNA abundance. Butter, relative to margarine, coconut and soybean oils, significantly increased serum non-HDL cholesterol concentrations. Endogenous and exogenous LCAT, CETP, and PLTP activities did not differ in hamsters fed margarine or saturated fat diets, despite lower hepatic LCAT, apo A-I, and SR-B1 mRNA abundance, suggesting that changes in available substrate and/or modification to the LCAT protein may have been involved in lipoprotein changes. These results suggest that lower HDL cholesterol concentrations, as a result of canola and soybean oil feeding, may not be detrimental due to increases in components involved in the reverse cholesterol transport process in these hamsters and may retard the progression of atherosclerosis.