Effect of long-term moderate physical exercise on plasma lipoproteins. The National Exercise and Heart Disease Project.

As part of the National Exercise and Heart Disease Project, 223 postcoronary men, aged 30 to 64, were randomly assigned to moderate exercise or control groups. Levels of total plasma cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, and triglycerides were measured. At baseline, alcohol intake, weight, and skin-fold thickness but not treadmill work capacity correlated with triglyceride or HDL cholesterol levels. After one year, no clinically important change in lipid levels was observed in either group. Using multiple regression analysis of the combined groups, changes in several independent variables, including work capacity change, were not predictive of changes in lipid levels. Thus, changes in levels of fitness and/or regular exercise did not substantially influence HDL cholesterol or other lipid levels.

Comparison of psyllium hydrophilic mucilloid and cellulose as adjuncts to a prudent diet in the treatment of mild to moderate hypercholesterolemia.

The effects of the administration of 5.1 g of psyllium or placebo (cellulose) twice daily for 16 weeks were compared as adjuncts to a prudent diet in the management of moderate hypercholesterolemia in a parallel, double-blind study. Psyllium decreased the total cholesterol level by 5.6% and the low-density lipoprotein cholesterol level by 8.6%, whereas the levels were unchanged in the placebo group. The high-density lipoprotein cholesterol level decreased during the diet stabilization period in both groups and returned to near-baseline values by week 16. Plasma triglyceride levels did not change substantially in either group. Subject compliance to treatment was greater than 95%. These data suggest that psyllium hydrophilic mucilloid in a twice-daily regimen may be a useful and safe adjunct to a prudent diet in the treatment of moderate hypercholesterolemia.

Effects of unopposed conjugated equine estrogen on lipoprotein composition and apolipoprotein-E distribution.

Administration of conjugated equine estrogen to 31 postmenopausal women for 3 months produced 14.6% and 9.4% decreases in low density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (apoB), and 11.5%, 12.7%, and 9.6% increases in high density lipoprotein cholesterol (HDL-C), apoA-I and apoA-II, respectively. Phospholipids of HDL2 and HDL3 were increased 57.9% and 19.3%, respectively, while relatively small increases in cholesterol of the two subfractions were not significant. Compositions of LDL and HDL and its subfractions were altered substantially with estrogen treatment. The proportion of LDL triglyceride to LDL-C was increased. The phospholipid content in both the HDL2 and HDL3 subfractions (compared to cholesterol) was increased significantly (34.8% and 10.7%, respectively), while the triglyceride content was increased only in the HDL2 subfraction (43.6%). Estrogen use also caused a 9.1% reduction in total apoE levels and a redistribution of apoE to the very low density lipoprotein (VLDL) from the LDL plus HDL fraction, resulting in a significant 19.5% decrease in apoE in the LDL plus HDL fraction. Changes in apoE in the VLDL fraction were associated positively with changes in the cholesterol levels of the VLDL fraction and inversely with changes in LDL-C and apoB levels, while changes in apoE in the LDL plus HDL fraction were associated positively with changes in the levels of HDL-C. Thus, estrogen causes alterations in lipoproteins that could potentially affect their metabolism and/or function.

Cyclic changes in lipoprotein and apolipoprotein levels during the menstrual cycle in healthy premenopausal women on a controlled diet.

Lipoprotein, apolipoprotein (apo), and hormone levels were measured in 12 healthy women over three consecutive menstrual cycles, one free-living and two under controlled dietary conditions. Serum hormone levels were measured to identify menstrual cycle phases (menses, early follicular, late follicular, and midluteal). After stabilization for one cycle on the controlled diet, ANOVA modeling of the second controlled-diet cycle revealed that low-density lipoprotein (LDL) cholesterol levels in the midluteal phase were significantly lower (by 7%) than in the early follicular phase. High-density lipoprotein (HDL) cholesterol levels during the late follicular phase were higher (by 6%) than menses levels. Differences in the HDL-cholesterol and apoA-I fluctuations resulted in a higher proportion of HDL-cholesterol to apoA-I during the late follicular phase than that during the menses phase. The ratios of LDL cholesterol/HDL cholesterol and apoB/apoA-I in the early follicular phase were greater by 5.6% and 6.0%, respectively, than those in the midluteal phase. Fluctuations in total cholesterol, triglyceride, apoA-I, and apoB did not reach significance. Thus, the cyclic fluctuations of LDL and HDL cholesterol need to be considered in the screening and medical monitoring of women with borderline lipoprotein levels, as well as in the design and the interpretation of results of studies involving premenopausal women.

Plasma lipid and lipoprotein concentrations of men consuming a low-fat, high-fiber diet.

This study assessed the influence of a low-fat, high-fiber diet on blood lipid concentrations of 42 men with desirable or moderately elevated cholesterol concentrations. A low-fat diet (19% fat, 4% saturated fatty acids, 4.6 g fiber/MJ) was compared with a high-fat diet (41% fat, 15% saturated fatty acids, 2.0 g fiber/MJ) and with subjects' self-selected diets. Substituting the low-fat for the high-fat diet decreased total, low-density-lipoprotein, and high-density-lipoprotein cholesterol by 17-20%. Lipid changes between 6 and 10 wk were minor. A reduction in plasma cholesterol of greater than 0.52 mmol/L was achieved with the low-fat diet in 59% of men changing from their self-selected diets and in 79% changing from the high-fat diet. Percent reduction was independent of subjects' cholesterol classification. Results indicate that significant reductions in plasma cholesterol can be achieved by the majority of men committing to a low-fat, high-fiber diet.

Dietary trans fatty acids: effects on plasma lipids and lipoproteins of healthy men and women.

Effects of cis and trans monounsaturated fatty acids (TFA) and saturated fatty acids were assessed in 29 men and 29 women consuming controlled diets. Subjects ate each diet for 6 wk in a Latin square design. The diets, each with 39-40% of energy as fat were: 1) high oleic (16.7% of energy as oleic acid), 2) moderate TFA (3.8% of energy as TFA), 3) high TFA (6.6% of energy as TFA), 4) and saturated (16.2% of energy as lauric+myristic+palmitic acids). Compared with the oleic diet, LDL cholesterol increased 6.0%, 7.8%, and 9.0% after moderate TFA, high TFA, and saturated diets, respectively. HDL cholesterol was unchanged after moderate TFA, but was slightly lower (2.8%) after high TFA. HDL cholesterol after the saturated diet was 3.5% higher than after the oleic diet. Changes in apolipoproteins B and A-I corresponded with changes in the lipoprotein cholesterols. Thus, compared with oleic acid, dietary TFAs raise LDL cholesterol, but to a slightly lesser degree than do saturates, and high TFA concentrations may result in minor reductions of HDL cholesterol.

Effects of margarine compared with those of butter on blood lipid profiles related to cardiovascular disease risk factors in normolipemic adults fed controlled diets.

Effects of butter and 2 types of margarine on blood lipid and lipoprotein concentrations were compared in a controlled diet study with 23 men and 23 women. Table spreads, added to a common basal diet, provided 8.3% of energy as fat. Diets averaged 34.6% of energy as fat and 15.5% as protein. Each diet was fed for 5 wk in a 3 x 3 Latin-square design. One margarine (TFA-M) approximated the average trans monoene content of trans fatty acid-containing margarines in the United States (17% trans fatty acids by dry wt). The other margarine (PUFA-M) was free of trans unsaturated fatty acids; it contained approximately twice the polyunsaturated fatty acid content of TFA-M (49% compared with 27% polyunsaturated fatty acids). The tub-type margarines had similar physical properties at ambient temperature. Fasting blood lipids and lipoproteins were determined in 2 samples taken from the subjects during the fifth week of each dietary treatment. Compared with butter, total cholesterol was 3.5% lower (P=0.009) after consumption of TFA-M and 5.4% lower (P< 0.001) after consumption of PUFA-M. Similarly, LDL cholesterol was 4.9% lower (P=0.005) and 6.7% lower (P< 0.001) after consumption of TFA-M and PUFA-M, respectively. Neither margarine differed from butter in its effect on HDL cholesterol or triacylglycerols. Thus, consumption of TFA-M or PUFA-M improved blood lipid profiles for the major lipoproteins associated with cardiovascular risk when compared with butter, with a greater improvement with PUFA-M than with TFA-M.

Lipoprotein and apolipoprotein levels in angiographically defined coronary atherosclerosis.

Recent studies suggest that apolipoproteins and subfractions of high-density lipoprotein (HDL) cholesterol may be better predictors of atherosclerotic coronary artery disease (CAD) than are plasma cholesterol and total HDL cholesterol. To examine this hypothesis, plasma cholesterol and triglyceride, cholesterol of low-density lipoprotein, HDL and its subfractions 2 and 3, apolipoprotein A-I, the apolipoprotein B of low-density lipoprotein, the ratio of apolipoprotein EII to EIII, and ratios of several of these variables were measured in a selected series of 126 patients (83 men and 43 women) who underwent coronary angiography for suspected CAD. Mean values of many of these variables differed significantly between the men with CAD and the men without significant CAD, when controlled for age, use of beta blockers and diuretic drugs. Using multivariate logistic regression analysis, the only variable that made a significant independent contribution in predicting CAD in men was the ratio of HDL cholesterol to total plasma cholesterol (p less than 0.0001). The mean of this ratio was 0.17 +/- 0.01 mg/dl in the men with CAD and 0.23 +/- 0.02 mg/dl in the male controls. All men with ratios of less than 0.15 mg/dl had significant CAD, defined as 50% or greater luminal diameter narrowing of 1 or more of the major coronary arteries. No measurement was a significant univariate or multivariate predictor of CAD in the women, but the power to detect such predictors was reduced because of small group sizes. In conclusion, the ratio of HDL cholesterol to plasma cholesterol may be superior to many of the more recently described lipoprotein and apolipoprotein-derived predictors of CAD.

Effects of conjugated equine estrogen with and without three different progestogens on lipoproteins, high-density lipoprotein subfractions, and apolipoprotein A-I.

The effects of conjugated equine estrogen and subsequent cyclical progestogen supplementation on lipoprotein and apolipoprotein A-I levels were investigated in three groups of postmenopausal women. Unopposed conjugated equine estrogen (0.625 mg) lowered total cholesterol 4-8% and low-density lipoprotein (LDL) cholesterol 12-19% below pre-treatment levels in all three groups. Levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were increased 9-13 and 9-18%, respectively, with unopposed estrogen. The increase in HDL cholesterol was mainly due to increases in the high-density lipoprotein2 (HDL2) subfraction. Addition of medroxyprogesterone acetate, norethindrone acetate, or d,l-norgestrel at doses shown previously to provide protection against endometrial hyperplasia reversed some of the beneficial estrogen effects, reducing levels of HDL cholesterol 14-17%, HDL2 cholesterol 22-37%, and apolipoprotein A-I 11-15% from those obtained with unopposed estrogen. The LDL cholesterol levels fell 12-19% with unopposed estrogen but remained 7-12% below baseline when progestogens were added. These observations demonstrate that after 3 months of treatment, all three progestogens reversed some of the favorable effects of unopposed estrogen on lipoproteins but permitted a continued modest reduction in LDL cholesterol.

Estrogen replacement therapy and coagulation: relationship to lipid and lipoprotein changes.

OBJECTIVE: To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system. METHODS: Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40-60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test. RESULTS: Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = .006) and activity (P = .001) and total protein S (P = .003) and a significant increase in protein C antigen (P = .017). C4b-binding protein also decreased significantly from baseline to 3 months (P < .001). Mean fibrinogen level decreased by 18.2 mg/dL, not a statistically significant change (P = .213). Estrogen produced the expected statistically significant changes in lipids and lipoproteins. Several correlations between changes in lipids and lipoproteins and coagulation indices were statistically significant. Protein C antigen and activity changes correlated directly with high-density lipoprotein cholesterol changes (r = .52, P < or = .005; r = .38, P < or = .05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = .54, P < or = .005). Triglyceride changes correlated directly with changes in protein C antigen (r = .36, P < or = .05) and activity (r = .49, P < or = .005) and inversely with C4b-binding protein (r = -.58, P < or = .01). Apoprotein B was correlated with free protein S (r = .48, P < or = .01). CONCLUSIONS: Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or by the addition of various progestins.

Quantitative and qualitative changes in lipids, lipoproteins, apolipoprotein A-I, and sex hormone-binding globulin due to two doses of conjugated equine estrogen with and without a progestin.

OBJECTIVE: To determine whether the quantitative and qualitative effects on lipoproteins differ between two doses of conjugated equine estrogen before and after progestin administration. METHODS: We randomized 103 postmenopausal women into a control group and into two groups receiving either 0.625 mg or 1.25 mg of conjugated equine estrogen for 4 months and then the same estrogen dose plus cyclic medroxyprogesterone acetate for 8 months. RESULTS: Both estrogen doses similarly lowered (P < .01) low-density lipoprotein (LDL) cholesterol and raised (P < .01) high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I, triglyceride levels of all lipoproteins, and sex hormone-binding globulin capacity. Cyclic addition of the progestin reduced HDL cholesterol (P < .01) and apolipoprotein A-I (P < .05), but not LDL cholesterol in either estrogen group. A greater lowering of HDL cholesterol (P < .05) in response to the progestin was seen with the 0.625-mg dose of estrogen. Estrogen-induced triglyceride enrichment of HDL and LDL was not reversed by the progestin. CONCLUSION: The only significant quantitative difference in lipoprotein levels between the doses of conjugated equine estrogen before or after administration of medroxyprogesterone acetate was a greater decline in HDL cholesterol levels with the lower dose after 4 months of the progestin. This difference was not sustained over time. There were no differences between doses in the estrogen-induced triglyceride enrichment of lipoproteins, and these qualitative changes were not affected by the progestin.

Progestins and oral contraceptive-induced lipoprotein changes: a prospective study.

In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for one year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups (p less than 0.05). ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol (LDL-C), a 13% fall in high density lipoprotein cholesterol (HDL-C) and a 27% decline in HDL2 cholesterol (HDL2-C) (p less than 0.05). Apoprotein A-I (Apo A-I) increased by 9% with ENA and by 11% with EED (p less than 0.05), but did not change significantly with ENG. This prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasma lipoproteins.

PIP: In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for 1 year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups. ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol, a 13% fall in high density lipoprotein cholesterol and a 27% decline in high density lipoprotein-2 cholesterol. Apoprotein A-1 increased by 9% with ENA and by 11% with EED, but did not change significantly with ENG. Khis prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasms lipoproteins.

Corn oil and beef tallow elicit different postprandial responses in triglycerides and cholesterol, but similar changes in constituents of high-density lipoprotein.

OBJECTIVE: The study was designed to compare, in a homogeneous, normolipidemic population, the postprandial responses of plasma lipids, in particular, high-density lipoprotein (HDL) constituents, after administration of a polyunsaturated fat and a more saturated fat. METHODOLOGY: Emulsions of 100 g corn oil (CO) and 100 g beef tallow (BT) were given in a crossover protocol to 12 male subjects (21-24 years). Plasma cholesterol (TC), triglycerides (TG), and HDL lipid and protein constituents were measured at 0, 2, 4, 7 and 10 hours. RESULTS: A postprandial increase in TG at 2 hours after CO ingestion (96%) was twice that with BT (48%); TG returned to near fasting levels at 10 hours after ingestion of either fat. Areas under the TG response curves for CO and BT were 6.29 +/- 1.67 and 1.75 +/- 0.60 mmol x hour/L (mean +/- SE), respectively. TC and low-density lipoprotein cholesterol (LDL-C) levels were unchanged at 10 hours after CO ingestion, but they were increased 8.1% and 9.3%, respectively, with BT. Both fats increased HDL TG at 2-4 hours, and both similarly increased HDL free cholesterol, cholesterol ester, phospholipid, apolipoproteins A-I and A-II, and lipoprotein (A-I) levels at 7-10 hours. Changes in HDL were predominantly in HDL3. CONCLUSIONS: The increase in LDL-C with BT at 10 hours suggests that levels may be abnormally elevated in "fasting" samples, dependent on the amount and type of fat in a prior meal. The increase in LDL-C is consistent with short-term regulation of hepatic LDL-receptor activity and/or LDL synthesis. Similar increases in HDL constituents at 7-10 hours after CO or BT, despite the difference in TG responses, suggests differences in the metabolism of chylomicrons and/or HDL due to the type of fat ingested.

Binding, uptake, and metabolism of chylomicron remnants by hepatocytes from control and chronic ethanol-fed rats.

Chylomicron remnants, but not lymph chylomicrons, showed a receptor-dependent high affinity saturable binding to normal rat hepatocytes. The Scatchard analysis of the specific binding data showed a high affinity binding site for the remnants with a dissociation constant of 0.61 nM, assuming a molecular weight of 50 X 10(6) for chylomicron remnants. Based on the heparin-releasable bound radioactivity, approximately 80% of the bound remnants seemed to be internalized. The binding process was markedly inhibited by pronase as well as by protein synthesis inhibitors. Competitive binding studies revealed that the order of competition for the binding of labeled remnants by homologous unlabeled lipoproteins was remnants greater than chylomicrons greater than very low density lipoproteins greater than high density lipoproteins. Human low density lipoproteins showed virtually no competition. Studies on the catabolism of triacylglycerol moiety of the remnants showed that 15.2% of the 14C label in the triacylglycerol moiety of the remnants was catabolized by the hepatocytes to 14CO2 due to specific interaction. This amounted to 93% of the total 14CO2 evolution. This was in sharp contrast to the catabolism of the triacylglycerol moiety of very low density lipoproteins from human and rat, where most of the 14CO2 evolution was due to pathways associated with nonspecific binding. Chronic ethanol feeding caused a 29% (p less than 0.02) decrease in the dissociation constant of the high affinity binding site of the liver cell for the remnants, whereas the extent of internalization was decreased by 19% (p less than 0.01) as compared to the pair-fed control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of lipogenesis in isolated hepatocytes by triglyceride-rich lipoproteins.

Very low density lipoproteins, chylomicrons, and remnants caused, within an hour, significant inhibition of fatty acid synthesis but not cholesterol synthesis in hepatocytes isolated from meal-fed rats. In contrast, low density lipoproteins, high density lipoproteins, and the serum fraction of density greater than 1.21 failed to significantly inhibit either fatty acid or cholesterol synthesis within 1 h. The Scatchard plots of specific binding showed that rat and human very low density lipoproteins interact with the high affinity sites on the hepatocytes with the apparent dissociation constants of 64 and 106 nM, respectively. These data also indicated that each hepatocyte was capable of binding 6 X 10(5) molecules of very low density lipoproteins.

Factors affecting the reassociation and reactivation of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase.

The pigeon liver fatty acid synthetase complex (14 S) is dissociated in low ionic strength buffer containing dithiothreitol to form a half-molecular weight subunits (9 S) which are completely inactive for the synthesis of saturated fatty acids. The dithiothreitol-protected (reduced) subunits are rapidly reassociated and reactivated to form the active enzyme complex, not only by an increase in salt concentration but also by micromolar concentrations of NADP+ or NADPH. Increases in KCl or NADPH concentration result in an increase in the extent of reactivation (equilibrium) with no change in the over-all rate of the reaction or the half-life ofreactivation of the enzyme. The extent (equilibrium) of reactivation of the enzyme is the same in 0.2 M potassium phosphate buffer, pH 7.0; 0.2 M KCl in 5 mM Tris-35 mM glycine buffer, PH 8.3; and 50 muM NADP+ or NADPH in the Tris-glycine buffer. The extent and rate of reactivation of the enzyme is dependent not only on ionic strength and NADPH concentration, but also on pH and temperature. Reactivation with 0.2 M KCl is optimal between pH 7.3 and 8.5. At higher and lower pH values the rate and extent of reactivation are lowered. The rate and extent of reactivation are also decreased as the temperature is lowered below 10 degrees. At 0 degrees there is little reactivation of enzyme activity. However, in the presence of 0.2 M KCl containing 15 to 40% glycerol at 0 degrees, reactivation of the enzyme is about 50% complete. The rate of reactivation of enzyme in the presence of KCl or NADPH conforms to first order kinetics. This result suggests that the subunits first combine to form an inactive complex which is subsequently transformed to an enzymatically active complex. Evidence for the presence of inactive complex was obtained in experiments carried out in 0.2 M KCl at pH 6.0, and in 0.2 M KCl at pH 8.3, at both 6 and 3 degrees. Under these conditions the amount of complex observed upon ultracentrifugation was greater than expected from determinations of enzyme activity. The above findings suggest that ionic and hydrophobic interactions, and possibly the water structure surrounding the interacting sites, are of prime importance in reassociation and reactivation of enzyme. In addition, NADP+ and NADPH have very specific effects in bringing about reassociation and in maintaining the structural integrity of the multienzyme complex.

Changes in women's plasma lipid and lipoprotein concentrations due to moderate consumption of alcohol are affected by dietary fat level.

We studied the impact of substituting ethanol for dietary carbohydrate, in high- and low-fat diets, on plasma lipids and lipoprotein concentrations. During a 12-wk, weight maintaining, controlled feeding study, women consumed only food and beverage provided by the Human Studies Facility of the USDA Beltsville Human Nutrition Research Center. Twenty-six women (age 41-59 y) consumed either a high-fat diet (38% of energy from fat) or a low-fat diet (18% of energy from fat) for 12 wk. The 12-wk feeding period was divided into two 6-wk periods in a cross-over design during which either ethanol or carbohydrate was added to the diet (5% of total daily energy intake). When the women consuming the high-fat diet had ethanol added to their diet, they had 6% lower plasma cholesterol (P = 0.003), 11% lower LDL cholesterol (P = 0.001) and 3% higher HDL cholesterol (P = 0.06) than when they had an equal amount (% energy) of carbohydrate added to their diet. The greater HDL cholesterol concentration was due to a 21% greater the HDL(2) subfraction (P = 0. 001). The ratio of LDL to HDL cholesterol was 14% lower. No significant differences existed in plasma lipids in women consuming the low-fat diet between the periods in which they had ethanol or carbohydrate added to their diet. This study suggests that the decreases in cardiovascular disease risk factors typically seen with moderate alcohol consumption may not be evident in individuals consuming a diet low in fat. Therefore changes in the risk factors associated with a low-fat diet and moderate alcohol consumption do not appear to be additive.

alpha-Tocopherol concentrations in plasma but not in lipoproteins fluctuate during the menstrual cycle in healthy premenopausal women.

Because premenopausal women experience cyclic fluctuations of plasma carotenoids and their lipoprotein carriers, it was hypothesized that plasma alpha-tocopherol (A-T) fluctuates by phase of the menstrual cycle. Twelve free-living women, with a confirmed ovulatory cycle, were given a controlled diet for two consecutive menstrual cycles. Blood was drawn during the menses, early follicular, late follicular and luteal phases to simultaneously measure serum hormones, plasma lipoproteins and A-T concentrations, and A-T distribution in the lipoprotein fractions. Plasma A-T concentrations were significantly lower during menses than during the luteal phase by approximately 12% in each controlled diet cycle (P < 0.001). Adjustment for serum cholesterol and triglyceride concentrations did not alter these findings. The distributions of A-T in lipoprotein cholesterol fractions were not significantly different by menstrual phase. From 61 to 62% of A-T was concentrated in the LDL fraction, with another 9-14% in HDL2, 17-22% in HDL3 and the remaining 6-8% in VLDL+ IDL. There were no significant differences in lipoprotein cholesterol fractions by menstrual phase, except for a significant increase (P = 0.03) in HDL2 cholesterol from the early follicular to the late follicular phase. Spearman rank correlations from data during the second controlled diet month showed A-T in HDL2 in the late follicular phase was positively correlated with HDL cholesterol in the early follicular (r = 0.88), late follicular (r = 0.86) and luteal phases (r = 0.86) and with luteal apolipoprotein (ApoA-1) level (r = 0.90), and luteal HDL2 cholesterol (r = 0.83). A-T in HDL3 in the early follicular phase was negatively correlated with HDL2 cholesterol (r = -0.96) and ApoA-1 (r = -0.85), whereas luteal A-T in HDL3 was correlated with luteal HDL3 cholesterol (r = -0.79). Late follicular A-T in VLDL was positively correlated with early follicular HDL3 cholesterol and late follicular HDL3 cholesterol (r = 0.83). Fluctuations of A-T concentrations by phase of the menstrual cycle should be taken into consideration in future research concerning premenopausal women and the risk of chronic disease.

Role of high density lipoproteins in regulation of hepatic fatty acid synthesis by chylomicron and very low density lipoprotein remnants.

High density lipoproteins (HDL) have been implicated in the transformation of native triglyceride-rich lipoproteins into their corresponding remnant particles during the action of peripheral lipoprotein lipase. The subsequent metabolism of these remnant particles by the liver results in the inhibition of hepatic lipogenesis. In the present study, remnant particles of chylomicrons or very low density lipoproteins (VLDL) have been generated in the perfused heart system both in the absence and presence of HDL. These have been characterized chemically, and the effects of both native lipoproteins and their respective remnants on fatty acid synthetic rates of hepatocytes have been assessed. Thirty to sixty-six per cent of the triglyceride moieties of native lymph chylomicrons or VLDL were hydrolyzed during a 45-min heart perfusion whether or not HDL was present in the perfusion media. Chylomicron remnants produced in the absence of HDL (25-300 micrograms/ml) caused only 10-20% inhibition of hepatic fatty acid synthesis, whereas remnants produced in the presence of HDL caused up to 78% inhibition at equivalent protein concentrations. The nonsuppressive remnants (produced in the absence of HDL) were converted to suppressive remnants upon incubation with HDL. Similar results were obtained with VLDL remnants produced in the absence and presence of HDL. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis apoprotein profiles of the nonsuppressive and suppressive remnants indicated a marked loss of the C apoproteins during the conversion of native chylomicrons or the nonsuppressive remnants to the suppressive remnants. Thus, HDL seems to be required for the removal of apoprotein C during the transformation of triglyceride-rich lipoproteins to the suppressive remnants. There was, however, no enrichment of apo-E on the suppressive remnant particles. We, thus, could not verify the suggested role of HDL in enriching the suppressive remnants with apoproteins E.