Low density and high density lipoprotein turnover following portacaval shunt in swine.

Turnover of 125I-low density lipoprotein (LDL) and of 131I-high density lipoprotein (HDL) was determined before and after end-to-side portacaval shunt in eight swine. LDL (d 1.019-1.063) and HDL (d.1.09-1.21) were isolated by ultracentrifugation and iodinated by the iodine monochloride technique. Immediately postoperatively there was no consistent change in the fractional catabolic rate (FCR) of LDL compared to preoperative control values, while in all animals FCR of HDL was significantly increased (by as much as 300%). After recovery from surgery, neither LDL nor HDL catabolic rates were significantly elevated above control values in four swine. However, plasma levels of LDL and HDL protein, and of LDL and HDL cholesterol were significantly reduced 10-12 weeks after the portacaval shunt. The reduced levels of LDL and HDL associated with normal fractional clearance rates imply a reduction in synthesis of LDL and HDL following portal diversion.     

Seasonal variation in plasma lipids, lipoproteins, apolipoprotein A-I and vitellogenin in the freshwater turtle, Chrysemys picta.

An analysis of plasma lipids and lipoprotein fractions was performed over the course of the annual ovarian cycle of the female turtle, Chrysemys picta. Determinations of total plasma triglycerides, cholesterol, vitellogenin and apolipoprotein A-I (apoA-I) were made. The lipid and protein composition of the lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and very high density lipoprotein (VHDL)] were also observed over the same period. Plasma triglyceride and vitellogenin levels were significantly increased in the spring preovulatory period and fall recrudescent phase. Total plasma cholesterol levels were significantly elevated only at the onset of the fall recrudescent phase and apoA-I levels were highest during the postoviposition/ovarian arrest phase. The triglyceride content of VLDL was highest in preovulatory animals and there were apparent seasonal changes in the expression of apoA-I and apoE of HDL/VHDL. We conclude that the coordinate regulation of lipids and protein contributes to seasonal ovarian growth and clearance of lipids from plasma, both of which are most likely under hormonal control.     

Variations in Body Composition and Plasma Lipids in Response to a High‐Carbohydrate Diet

Objective: To examine the extent to which variations in body composition modulate changes in the lipid profile in response to the ad libitum consumption of a diet rich in carbohydrates (CHOs) (high‐CHO diet: 58% of energy as CHOs) or high in fat and in monounsaturated fatty acids (MUFAs) (high‐MUFA diet: 40% of energy as fat, 23% as MUFAs). Research Methods and Procedures: Sixty‐three men were randomly assigned to one of the two diets that they consumed for 6 to 7 weeks. Body composition and fasting plasma lipid levels were measured at the beginning and the end of the dietary intervention. Results: The high‐CHO and high‐MUFA diets induced significant and comparable reductions in body weight and waist circumference. These changes were accompanied by significant and comparable (p < 0.01) reductions in total plasma cholesterol and low‐density lipoprotein cholesterol levels. However, the high‐MUFA diet had more beneficial effects on plasma triglyceride concentrations (p < 0.01) and on plasma high‐density lipoprotein cholesterol levels (p = 0.02) compared with the high‐CHO diet. Diet‐induced changes in waist circumference were significantly associated with changes in low‐density lipoprotein cholesterol levels in the high‐CHO group (r = 0.39, p = 0.03) but not in the high‐MUFA group (r = 0.16, p = 0.38). Discussion: Improvements in plasma lipids induced by the ad libitum consumption of a high‐CHO diet seem to be partly mediated by changes in body weight, whereas lipid changes induced by the high‐MUFA diet seem to be independent of changes in body weight.     

Evaluation of gel chromatography for plasma lipoprotein fractionation

The fractionation of lipoproteins of normal and hyperlipidemic subjects on a column of 2% agarose was compared with ultracentrifugation and paper electrophoresis procedures. The following results were obtained. (a) Plasma lipoproteins were eluted successively from the column in the four overlapping peaks of chylomicrons, very low density lipoproteins, low density lipoproteins, and high density lipoproteins. (b) Very low density lipoproteins and high density lipoproteins (d > 1.063, containing nonlipoprotein proteins) showed continuous progressive changes in lipid composition as these fractions emerged, while low density lipoproteins showed a relatively constant lipid composition. (c) A discontinuous transition of lipid composition was observed when consecutive ultracentrifugal fractions were placed on the column. (d) The "trail" of pre-beta lipoprotein seen on paper electrophoresis was shown to consist of particles whose molecular sizes range between chylomicrons and pre-beta lipoproteins. A reverse relationship was observed between electrophoretic mobilities of "trail" components and their particle size. (e) Gel with an agarose content of 2% seemed to fractionate chylomicrons and very low density lipoproteins more effectively than other lipoprotein classes.     

Changes in plasma lipids and lipoprotein cholesterol during a high altitude mountaineering expedition (4800 m)

Effects of high altitude exposure on plasma lipids and lipoprotein cholesterol were studied in 8 mountaineers who spent 3 weeks at the Annapurna IV base camp (4800 m) after a 12 day trek. In spite of the moderate physical exertion at the camp, the loss of body weight was more pronounced during the stay at high altitude than during the trekking period. Compared with baseline values observed at sea level, marked reductions in plasma cholesterol (-27%) and phospholipids (-19%) were found 3 days after arrival at the camp and persisted during the next 17 days. A less marked fall in plasma triglycerides occurred, weakly significant at the end of the stay. Because there were no relevant changes in very low density lipoproteins or in high density lipoprotein (HDL)-cholesterol, the low plasma cholesterol levels at the high altitude resulted mainly from the reduction in low density lipoprotein (LDL)-cholesterol: the mean HDL/LDL cholesterol ratio changed from 0.39 at sea level to 0.63 at the end of the stay at 4800 m. Fluctuations in LDL-cholesterol were not concomitant with those in body weight and were independent of the exercise training during the expedition. This study shows moreover that the early drop in LDL-cholesterol was associated with an opposite change in plasma levels of catecholamines and thyroid hormones. Taking into account that such hormonal responses are classically observed at high altitude, the concomitant decrease in LDL-cholesterol might be interpreted as being a relevant adaptative response to hypoxic conditions at high altitude.     

Dose and duration effects of estradiol valerate on serum and lipoprotein lipids

Non-alkylated estrogens, like estradiol valerate (F2V), are widely used in the treatment of the postmenopausal hormonal deficiency syndrome. Their effects on serum and lipoprotein lipids are characterized by an increase in the lipid constituents of high density lipoproteins (HDL) and, usually, a decrease in low density lipoproteins (LDL). These effects are considered beneficial as regards atherogenesis and the risk for cardiovascular diseases. Unlike the effects of alkylated estrogens, no concomitant increase in triglycerides (TG) in serum and very low density lipoproteins (VLDL) - adverse effects - are seen in doses of up to 2 mg E2V. In order to compare the effects of 2 and 4 mg of E2V on serum and lipoprotein lipids, 19 bilaterally oophorectomized women participated in a cross-over study after a 4 week long wash-out period. To evaluate the influence of the time factor, 10 of the women continued taking 2 mg and 9 taking 4 mg of E2V respectively for an additional period of 12 weeks, resulting in a total treatment period of 24 weeks per group. The serum lipoproteins were separated by preparative ultracentrifugation, the serum and lipoprotein lipids being assessed using commercially available kits. In the cross-over part of the study, total (TC) and free cholesterol (FC) and phospholipids (PL) increased in HDL and decreased in LDL. Neither dose increased TG in serum or VLDL. These changes in the lipoprotein pattern persisted at the end of the entire study. Consequently, within the range of commonly used doses (2 and 4 mg) E2V seems to have a constant and, in terms of cardiovascular disease, favourable influence on lipoprotein metabolism irrespective of doses and periods studied.     

A preliminary report on the feeding of cynomolgus monkeys (Macaca fascicularis) with a high-sugar high-fat diet for 33 weeks

Background The metabolic syndrome is common in populations exposed to a typical Western diet. There is a lack of an animal model that mimics this condition. Methods We fed 15 cynomolgus monkeys ad libitum a high‐sugar high‐fat (HSHF) diet for 33 weeks. Body weight, body composition, serum lipids, and insulin were measured at baseline and at 33 weeks. Results The animals tolerated the HSHF diet very well. In the intervention group, total serum cholesterol and low‐density lipoprotein cholesterol were 3‐ and 5‐fold higher, respectively, at 33 weeks as compared with their baseline levels. Serum high‐density lipoprotein cholesterol and triglycerides were not significantly affected. Dual‐energy X‐ray absorptiometry (DXA) analysis of the intervention group indicated that the trunk fat mass increased by 187% during this period. Conclusions Cynomolgus monkeys should be a useful model for investigating the interactions of diet and other factors such as genetics in the development of the metabolic syndrome.     

Early changes in plasma lipoprotein structure and biosynthesis in cholesterol-fed rabbits

Plasma lipoproteins of d < 1.063 g/ml from rabbits fed a diet containing 1% cholesterol for 4 days showed changes in concentration and rates of flotation as determined by analytical ultracentrifugation. A marked increase in cholesteryl ester content of lipoprotein with d < 1.019 g/ml was the most prominent change in rabbits fed the diet for 21 days. Gel electrophoresis and immunochemical procedures demonstrated that in control and hypercholesterolemic rabbits there were some common apolipoproteins found in all lipoproteins with density < 1.063 g/ml. In control rabbits, there were also apolipoproteins specific to the lipoprotein fraction with d < 1.019 and to the fraction with d 1.019-1.063 g/ml. However, in rabbits fed the hypercholesterolemic diet for 21 days, the apolipoproteins characteristic of fraction 1.019-1.063 were the most abundant in the fraction with d < 1.019 g/ml. Liver slices from rabbits fed the high cholesterol diet for 7 and 21 days incorporated more l-[(14)C]leucine into very low density and low density lipoproteins than controls. The results suggest that cholesterol feeding leads to an increase in biosynthesis of lipoproteins with d < 1.063 g/ml. The newly synthesized lipoprotein contains apolipoproteins similar to those found in controls but with a higher lipid-to-protein ratio. From the apoprotein composition, it is concluded that the very low density fraction present in cholesterol-fed animals is more structurally related to low density lipoproteins than to the very low density lipoproteins isolated from control animals.     

Post-heparin hepatic lipase activity and plasma high density lipoprotein levels in men during physical training

Plasma post-heparin hepatic lipase (PHHL) activity, plasma lipids, and high density lipoprotein cholesterol (HDL-C) levels, pulse rate at submaximal workload, and body weight were measured in 12 men during the 18 weeks physical training for their first marathon run. Reduced pulse rate at submaximal workload indicated that the men increased their physical fitness during the training period. Plasma HDL-C levels (+27%) and PHHL activity (+29%) also increased significantly after 18 weeks training. These changes were not in accord with the inverse correlation between plasma HDL-C levels and PHHL activity which was observed before training. The results of this study do not support the concept that reduced PHHL activity is mainly responsible for increased levels of plasma HDL-C with training.     

12周高强度间歇训练对不同基因型载脂蛋白E血脂异常人群的调脂作用

目的:观察12周高强度间歇训练(HIIT)对不同载脂蛋白E(ApoE)基因型血脂异常人群的血脂调节作用。方法:通过测试空腹血脂指标,筛选出88例血脂异常患者作为受试对象,采集受试对象口腔粘膜进行载脂蛋白E基因型检测,测定12周高强度间歇训练干预前后的血脂水平。结果:88例血脂异常者中共检测出5种基因型,其分布为ApoE3/3＞ApoE3/4 ＞ApoE2/3＞ApoE2/2＞ApoE2/4,等位基因ε3＞ε2=ε4。运动干预前,血脂异常人群中ε4等位基因组的总胆固醇水平显著高于ε2和ε3基因组(P＜0.01),低密度脂蛋白胆固醇水平显著高于ε2基因组(P＜0.05),其余指标在各组间无显著性差异(P＞0.05)。12周的高强度间歇训练显著降低ε3基因组血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平。ε4基因组在运动干预后血清总胆固醇和低密度脂蛋白胆固醇降低,甘油三酯和高密度脂蛋白胆固醇无显著性改变。ε2基因组在运动干预后血清脂质无明显改善。结论:血脂异常人群载脂蛋白E基因多态性影响运动的调脂效果,12周高强度间歇训练可以作为ε3和ε4等位基因携带者调节血脂的运动干预方式。     

A simple and sensitive method for lipoprotein and lipids profiles analysis of individual micro-liter scale serum samples

A simple and sensitive method to determine lipoprotein and lipids profiles in micro-liter scale individual serum sample is not presently available. Traditional lipoprotein separation techniques either by ultra-centrifugation or by liquid chromatography methods have their disadvantages in both lipoprotein separation and lipids component quantification. In this study we used small volume needing size-exclusion fast protein liquid chromatography to separate different lipoprotein subclasses in 50μL serum. And lipids contents, such as cholesterol, cholesterol ester and triacylglycerol, were measured by using two different fluorescence-based lipid detection methods. With this method, very low density lipoprotein, low density lipoprotein and high density lipoprotein could be easily separated, and follow-up lipid detection was completed by simple kinds of reactions. Serum lipoprotein and lipids profiling from C57BL/6 mice (n=5) and human (n=5) were analyzed. The elution profiles of five individuals were highly reproducible, and there were lipoprotein and lipids distribution variations between C57BL/6 mice and human beings. In conclusion, this method which combined small volume needing size-exclusion fast protein liquid chromatography and fluorescence-based lipids measurement, provided a simple, efficient, integrity and reproducible procedure for determining serum lipoprotein and lipids profiles in micro-liter scale levels. It becomes possible that determination of lipoprotein profiles and gaining information of lipids in different lipoproteins can be accomplished simultaneously.     

The effects of 20 days bed rest on serum lipids and lipoprotein concentrations in healthy young subjects

The effects of 20 days bed rest (BR) on serum lipids and lipoprotein concentrations were investigated in 23 healthy young subjects (13 males and 10 females, aged 19 to 25 yr.). After 20 days BR, VO2max was reduced in both genders, but body composition did not change. The ratio of glucose area to insulin area during an oral glucose tolerance test decreased gradually throughout BR, which suggested a decrease in insulin sensitivity. Estimated changes in plasma volume from the beginning of BR were largest at day 3 of BR (-9.1% in females and -3.4% in males) and seemed to return the initial level at the end of BR in both genders. The increase in serum triglycerides and the decrease in high density lipoprotein (HDL) cholesterol, and apolipoprotein AI were observed in both genders during BR. In a smaller study of 4 males and 5 females, 20 days BR was associated with a decrease in HDL, cholesterol, a decrease in apolipoprotein AI and apolipoprotein AII, decrease in a plasma postheparin lipoprotein lipase activity and an increase in very low density lipoprotein triglyceride. Overall, the data suggested that the decrease in lipoprotein lipase activity and insulin sensitivity may contribute to the impairment in HDL metabolism.     

Plasma lipoproteins of free-ranging howling monkeys (Alouatta palliata)

1. Plasma lipids and lipoproteins of free-ranging howling monkeys from Costa Rica (Alouatta palliata), aged 5 months to 23 years, were characterized. 2. High density lipoproteins were lipid-rich, similar to HDL2 of human plasma. 3. Fatty acid compositions of major lipid classes of very low, low and high density lipoproteins differed among social groups, possibly due to both dietary and genetic factors. 4. Low and high density lipoprotein phospholipids were enriched in phosphatidylethanolamine. 5. Howler plasma cross reacted with antihuman apoA-I antibodies but not with antihuman LDL antibodies. 6. No dimeric form of apoA-II was present, unlike human apoA-II.     

Effects of dietary monounsaturated fatty acids on plasma lipids in humans

In order to test whether monounsaturated fatty acids (MUFA, M) would lower plasma cholesterol and/or triglycerides (TG), 14 young men were studied in a metabolism ward. They were given two experimental diets with the same P/S ratio (P: polyunsaturated; S:saturated fatty acids) but different P + M/S ratios in composition of dietary fatty acids. Six men were in experiment I. In two groups of three, each group was given either the high or the low P + M/S ratio diet for 6 weeks. In experiment II, two groups of four men were subjected to a 3-week cross-over feeding trial (total of 6 weeks). We found in the crossover study that when the dietary P/S ratio was fixed at 1.0, those subjects given a diet with the higher P + M/S ratio of 4.5 showed significantly higher plasma total TG, very low density lipoprotein (VLDL)-TG, low density lipoprotein (LDL)-TG, and LDL-cholesterol than when given a diet with a lower P + M/S ratio of 1.5. Plasma total cholesterol, apoprotein A-I, and apoprotein B-100 were not significantly different between the two dietary periods. Plasma fatty acid patterns showed a significantly higher plasma MUFA level during the period of a higher P + M/S diet. In contrast to some recent reports, our studies indicate that a large amount of dietary MUFA may raise some fractions of plasma lipids in humans.     

Influence of dietary trans-fatty acids on swine lipoprotein composition and structure.

Four groups of 20 weanling swine each were fed either (a) basal diet, (b) basal plus hydrogenated fat (13% trans), (c) basal plus hydrogenated fat (13% trans) and 0.4% cholesterol, or (d) basal plus beef tallow (all cis). After six months of feeding, the animals were killed and the blood and aortas were removed. Very low density, low density, and high density lipoproteins were then isolated from the plasma by ultracentrifugal flotation. Although the fatty acid composition of the basal diet was different from the diets supplemented with either hydrogenated fat containing trans-fatty acid or beef tallow containing all cis, the lipid and fatty acid compositions of each of the isolated lipoprotein classes for the four groups of animals were remarkably similar. Elaidate was clearly incorporated into the lipoproteins of animals fed hydrogenated fat, but the level of incorporation was generally less than 5%. In a direct comparison of the structure of the lipoproteins from the different groups, we did not find any significant differences in their physical properties as determined by pyrene fluorescence and electron paramagnetic resonance methods. Grossly visible fatty streaks and fibrous plaques were not found in any of the swine aorta. However, light and electron microscopy indicated the presence of atherosclerotic lesions in the distal abdominal aorta and bifurcation. These studies demonstrate that a diet containing a substantial amount of trans-fatty acid leads to a small but definite incorporation into the swine lipoproteins. However, such changes had relatively little effect on lipoprotein structure or the presence of atherosclerotic lesions in these 6-month-old swine.     

Lipid and insulin levels in obese children: changes with age and puberty

Objective: The goal was to describe the lipid profile and insulin changes seen in obese children and adolescents at different stages of puberty. Research Methods and Procedures: A cross‐sectional study was conducted by chart review of 181 obese (BMI > 95th) children and adolescents 5 to 17 years of age, who were referred to the Center for Atherosclerosis Prevention for cardiovascular risk reduction from January 2003 through December 2003. Results: Eighty (44.2%) subjects were <12 years of age, and 101 (55.8%) were ≥12 years. Severity of obesity as expressed by BMI standard deviation score did not differ between these age groups. A significant difference with lower serum levels of total cholesterol, non‐high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol was seen with older age and with advancing sexual maturity rating. Triglycerides, very‐low‐density lipoprotein cholesterol, and lipoprotein(a) levels remained elevated across age and pubertal stages. Insulin levels and insulin resistance as expressed by homeostasis model assessment were significantly higher with older age. Similar trends were observed both in obese boys and obese girls during puberty. Discussion: The most striking findings of this study are that in the 5‐ to 17‐year‐old obese population, the combination of elevated triglycerides and very‐low‐density lipoprotein cholesterol and low high‐density lipoprotein cholesterol levels place them at greater cardiovascular risk than their non‐obese peers, even when the changing patterns of lipids and lipoproteins seen during pubertal maturation are accounted for.     

Characterization of equine plasma lipoproteins after separation by density gradient

1. Plasma lipoproteins from six thoroughbred horses were separated by density gradient ultracentrifugation. For each sample, lipoprotein bands were visualized by means of a prestained plasma control and characterized by electrophoretic, chemical and morphological analysis. 2. Very low density lipoproteins (VLDL) were isolated at d less than 1.018 g/ml. 3. Two clearly resolved bands were detected in the low density lipoprotein fraction (LDL). The density limits were evaluated as follows: LDL1(1.028 less than d less than 1.045 g/ml) and LDL2(1.045 less than d less than 1.070 g/ml). Marked differences were observed in the chemical composition and particle size of LDL1 and LDL2 fractions. 4. High density lipoprotein fraction (HDL) was usually isolated as a single band, distributed over the range 1.075 less than d less than 1.180 g/ml. However, chemical composition and particle size revealed heterogeneity in HDL subfractions. 5. The density limit of LDL and HDL bands varied in each animal, indicating differences in equine lipoprotein distribution.     

Plasma lipids and lipoproteins of some members of the order Perissodactyla.

1. The plasma lipoproteins of various members of the order Perissodactyla have been examined by electrophoresis and analytical ultracentrifugation. 2. In the Equidae, high density (alpha) lipoprotein was the major component (80-90%) and low density (beta) lipoprotein (10-20%) the minor component. 3. In the Tapiridae represented by the Malayan tapir (Tapirus indicus), high density and low density lipoproteins were present in approximately equal amounts. 4. In the Rhinocerotidae, the high density lipoprotein characteristic of the Equidae and Tapiridae was absent, and the plasma lipoproteins consisted of a complex group having beta mobility on electrophoresis and a flotation pattern usually associated with low density lipoprotein. 5. The fatty acid composition of plasma lipids was remarkably similar in all members of the Perissodactyla examined, with very high percentages of linoleic acid (greater than 70%) being found in the cholesteryl esters.     

Chemical characterization of the serum very low density and high density lipoproteins from bullfrog, Rana catesbeiana.

The chemical properties of very low density and high density lipoproteins of adult bullfrog serum were determined. This serum contained extremely low levels of both very low density lipoprotein (10-30 mg/100 ml) and high density lipoprotein (5-10 mg/100 ml). The constituents of very low density lipoprotein, on a weight percentage basis, were found to be 48.1% triglyceride, 17.3% cholesterol ester, 8.8% cholesterol, 11.6% phospholipid, and 12% protein. These constituents were also present in high density lipoprotein with weight percentage values of 3.7%, 19.3%, 11.9%, 25.2%, and 36.8%, respectively. The fatty acid compositions of the triglycerides, cholesterol esters, and phosphatidylcholine were quite similar in the very low density lipoprotein and high density lipoprotein. However, shingomyelin fatty acid composition was appreciably different in the two lipoproteins. Disc gel electrophoresis in sodium dodecyl sulfate-polyacrylamide gels produced patterns with one major (approximate molecular weight, 7,000) and several minor bands for the apoprotein of very low density lipoprotein and one major (approximate molecular weight, 28,000) and several minor bands for that of high density lipoprotein.     

Effects of estrogen administration on the lipoproteins and apoproteins of the chicken.

The plasma lipoproteins of estrogen-treated and untreated sexually immature hens have been compared with respect to their concentration in plasma, protein and lipid composition, particle size, and and apoprotein composition. Administration of diethylstilbestrol resulted in a 400-fold rise in the concentration of very low density lipoprotein (VLDL), a 70-fold rise in low density lipoprotein (LDL), and a marked reduction in high density lipoprotein (HDL) protein. It also resulted in the production of LDL and HDL which were enriched in triacylglycerol, while the proportion of cholesterol in all three lipoprotein fractions decreased. In contrast to the lipoproteins from untreated birds, lipoproteins of density less than 1.06 g/ml from estrogen-treated birds were not clearly separable into discrete VLDL and LDL fractions, but appeared to be a single ultracentrifugal class. The apoprotein composition of VLDL and LDL from untreated birds differed from each other; however, the apoprotein patterns of VLDL and LDL from estrogen-treated birds were indistinguishable: both contained a large amount of low molecular weight protein in addition to the high molecular weight component that predominates in the untreated state. The apoprotein composition of HDL was also markedly altered by estrogen administration: the 28,000 mol. wt. protein (apo A-I) decreased in amount from 65% to less than 5% of the total, while a low molecular weight (Mr = 14,000) protein and as yet poorly defined high molecular weight components became predominant. These observations indicate that the hyperlipidemia induced by estrogen administration is accompanied by marked alterations, both qualitative and quantitative, in the plasma lipoproteins.