Effect of cigarette smoking on high density lipoprotein phospholipids

The effect of acute inhalation of cigarette smoke on high density lipoprotein (HDL) phospholipid composition in White Carneau pigeons was examined. Four treatments included: 1) Shelf Control birds fed a chow diet and retained in their cages; 2) Sham pigeons fed a cholesterol-saturated fat diet and exposed to fresh air by a smoking machine; 3) Low nicotine-low carbon monoxide (LoLo) animals also fed the cholesterol diet and exposed to low concentrations of these cigarette smoke products; and 4) High nicotine-high carbon monoxide (HiHi) birds fed the cholesterol diet and subjected to high concentrations of these inhalants. The cholesterol-fat diet caused an increase in the concentration of most HDL phospholipid classes. Exposure to the HiHi regimen resulted in an increase in the HDL cholesterol/phospholipid ratio and a reduction in the concentration of HDL phosphatidyl ethanolamine, phosphatidyl serine/inositol, sphingomyelin and lysophosphatidyl choline. Cigarette smoking may thus attenuate HDL's anti-atherogenic properties by altering surface phospholipid components.     

Concentration and composition of serum lipoproteins during a low-fat diet at two levels of polyunsaturated fat

A 12-week dietary intervention was carried out among 40 families from North Karelia, a county in Finland with an exceptionally high rate of coronary heart disease and high serum cholesterol values. The proportion of dietary energy derived from fat was reduced during the 12-week intervention period from about 39% to 23% in all families. The families were randomly allocated into two groups. Twenty families consumed a diet with a polyunsaturated to saturated fat (P/S) ratio of 0.9 (group I), while the other 20 families had a diet with a P/S ratio of 0.4 (group II). Total serum cholesterol decreased by 16% and 9% in men of groups I and II, respectively, and by 16% in women of both groups. These changes were due to a decrease in both low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. LDL cholesterol and phospholipid reached minimum values after 6 weeks on both intervention diets, but LDL protein responded more slowly. Thus, after 6 weeks LDL had an altered composition containing less cholesterol and phospholipids and more protein and triglycerides than during the baseline diet. During the intervention, the linoleic acid content in the serum cholesteryl ester fraction increased, and the magnitude of this change correlated negatively with the changes in total and LDL cholesterol. The decrease in HDL cholesterol during the two intervention diets was due to a fall in the HDL2 cholesterol (29% and 24% in men, and 26% and 25% in women in groups I and II, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

High molecular weight poly-gamma-glutamic acid regulates lipid metabolism in rats fed a high-fat diet and humans

We investigated the effect of high molecular weight polygamma- glutamic acid (hm gamma-PGA) on adiposity and lipid metabolism of rats in the presence of an obesity-inducing diet. Thirty-two Sprague-Dawley rats were fed either a normal-fat (11.4% kcal fat, NFC) or high-fat (51% kcal fat, HFC) diet. After 5 weeks, half of each diet-fed group was treated with hm gamma-PGA (NFP or HFP) for 4 weeks. The HFC group had significantly higher body weight, visceral fat mass, fasting serum levels of total cholesterol, LDL cholesterol, and leptin, and lower serum HDL cholesterol level compared with those of the NFC group (p < 0.05). Treatment with hm gamma-PGA decreased body weight gain and perirenal fat mass (p<0.05), fasting serum total cholesterol, and mRNA expression of glucose-6- phosphate dehydrogenase (G6PD), regardless of dietary fat contents (p < 0.01). However, hm gamma-PGA increased serum HDL cholesterol in the HFC group (p < 0.05). In vitro, 3-hydroxy-3-methylglutaryl coenzyme-A (HMGCoA) reductase activity was suppressed by the addition of hm gamma-PGA. In agreement with observations in animal study, the supplementation of hm gamma-PGA (150 mg/day) to 20 female subjects in an 8-week double-blind, placebocontrolled study resulted in a tendency to decrease total cholesterol and LDL cholesterol concentrations. We thus conclude that dietary supplementation of hm gamma-PGA may act as a hypocholestrolemic agent, secondary to its inhibitor effect on HMG-CoA reductase, and decrease abdominal adiposity by decreasing hepatic lipogenesis. The present study is an important first step in establishing the effect of hm gamma-PGA on cholesterol levels in rats and humans.     

Dietary fat and cholesterol induced modification of minipig lipoprotein fluidity and composition.

1. Miniature swine were fed a low (2.7%) fat control stock diet alone or supplemented with either 20% lard plus 1% cholesterol or 20% lard alone for periods of up to 6 months. 2. Cholesterol feeding reduced VLDL fluidity drastically and LDL fluidity minimally but had no effect on HDL fluidity. 3. Lard feeding had no effect on lipoprotein fluidity. 4. The rigid VLDL produced by cholesterol feeding was enriched in cholesterol and phospholipid contents, similar to beta-VLDL. 5. Plasma cholesterol concentrations were increased by 1.5 to 5-fold in pigs fed stock diets supplemented with 20% lard, with or without added cholesterol, but plasma triacylglycerol concentrations were not affected by either diet modification. 6. Diet effects were complete within 4 weeks with no further changes for periods up to 6 months. 7. Regression of the induced hypercholesterolemia was also accomplished within one month of removing cholesterol from the diet.     

Influence of dietary lipids on hepatic mRNA levels of proteins regulating plasma lipoproteins in baboons with high and low levels of large high density lipoproteins.

Selective breeding of baboons has produced families with increased plasma levels of large high density lipoproteins (HDL1) and very low (VLDL) and low (LDL) density lipoproteins when the animals consume a diet enriched in cholesterol and saturated fat. High HDL1 baboons have a slower cholesteryl ester transfer, which may account for the accumulation of HDL1, but not of VLDL and LDL. To investigate the mechanism of accumulation of VLDL + LDL in plasma of the high HDL1 phenotype, we selected eight half-sib pairs of baboons, one member of each pair with high HDL1, the other member with little or no HDL1 on the same high cholesterol, saturated fat diet. Baboons were fed a chow diet and four experimental diets consisting of high and low cholesterol with corn oil, and high and low cholesterol with lard, each for 6 weeks, in a crossover design. Plasma lipids and lipoproteins and hepatic mRNA levels were measured on each diet. HDL1 phenotype, type of dietary fat, and dietary cholesterol affected plasma cholesterol and apolipoprotein (apo) B concentrations, whereas dietary fat alone affected plasma triglyceride and apoA-I concentrations. HDL1 phenotype and dietary cholesterol alone did not influence hepatic mRNA levels, whereas dietary lard, compared to corn oil, significantly increased hepatic apoE mRNA levels and decreased hepatic LDL receptor and HMG-CoA synthase mRNA levels. Hepatic apoA-I message was associated with cholesterol concentration in HDL fractions as well as with apoA-I concentrations in the plasma or HDL. However, hepatic apoB message level was not associated with plasma or LDL apoB levels. Total plasma cholesterol, including HDL, was negatively associated with hepatic LDL receptor and HMG-CoA synthase mRNA levels. However, compared with low HDL1 baboons, high HDL1 baboons had higher concentrations of LDL and HDL cholesterol at the same hepatic mRNA levels. These studies suggest that neither overproduction of apoB from the liver nor decreased hepatic LDL receptor levels cause the accumulation of VLDL and LDL in the plasma of high HDL1 baboons. These studies also show that, in spite of high levels of VLDL + LDL and HDL1, the high HDL1 baboons had higher levels of mRNA for LDL receptor and HMG-CoA synthase. This paradoxical relationship needs further study to understand the pathophysiology of VLDL and LDL accumulation in the plasma of animals with the high HDL1 phenotype.     

Study of the atherogenic dyslipoproteinemia induced by dietary cholesterol in rhesus monekys (Macaca mulatta).

Hypercholesterolemia was induced in adult male rhesus monkeys with a high-fat diet containing an elevated cholesterol level (0.5%). Plasma lipoproteins were chromatographically separated into four size populations (regions) that were subdivided by density until fractions with single electrophoretic mobilities were obtained. The region III lipoproteins (LDL) contained 80% of plasma cholesterol and were present in the highest concentration of all fractions. Their molecular weight was increased over that of controls so that each particle averaged 1.8 times the number of cholesteryl ester molecules as did control LDL. Region II lipoproteins, a heterogeneous group, were present in next highest concentration. Most were cholesteryl ester-rich, beta-migrating lipoproteins that overlapped the VLDL and LDL density ranges; apoB was the predominant apoprotein. One region II subfraction had pre beta 2 migration and the density range. 1.050 less than d less than 1.10. Another subfraction, cholesteryl ester-rich VLDL including only about 1% of plasma cholesterol, had pre beta 1 migration and apoB and apoC as the predominant apoproteins with no apoprotein E. Region I lipoproteins were larger sized, slow beta-migrating cholesteryl ester-rich VLDL that included 5% of plasma cholesterol. ApoB and apoE were the predominant apoproteins. Region IV lipoproteins (HDL) contained 4% of the plasma cholesterol; their concentration was decreased to about 1/3 of the control level. Atherogenic features of the diet-induced dyslipoproteinemia included the increased plasma concentrations and cholesteryl ester contents of the region I, II, and III lipoproteins in addition to the decreased HDL concentration.     

Lecithin:cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice.

The purpose of the present study was to test the hypothesis that lecithin:cholesterol acyltransferase (LCAT) deficiency would accelerate atherosclerosis development in low density lipoprotein (LDL) receptor (LDLr-/-) and apoE (apoE-/-) knockout mice. After 16 weeks of atherogenic diet (0.1% cholesterol, 10% calories from palm oil) consumption, LDLr-/- LCAT-/- double knockout mice, compared with LDLr-/- mice, had similar plasma concentrations of free (FC), esterified (EC), and apoB lipoprotein cholesterol, increased plasma concentrations of phospholipid and triglyceride, decreased HDL cholesterol, and 2-fold more aortic FC (142 +/- 28 versus 61 +/- 20 mg/g protein) and EC (102 +/- 27 versus 61+/- 27 mg/g). ApoE-/- LCAT-/- mice fed the atherogenic diet, compared with apoE-/- mice, had higher concentrations of plasma FC, EC, apoB lipoprotein cholesterol, and phospholipid, and significantly more aortic FC (149 +/- 62 versus 109 +/- 33 mg/g) and EC (101 +/- 23 versus 69 +/- 20 mg/g) than did the apoE-/- mice. LCAT deficiency resulted in a 12-fold increase in the ratio of saturated + monounsaturated to polyunsaturated cholesteryl esters in apoB lipoproteins in LDLr-/- mice and a 3-fold increase in the apoE-/- mice compared with their counterparts with active LCAT. We conclude that LCAT deficiency in LDLr-/- and apoE-/- mice fed an atherogenic diet resulted in increased aortic cholesterol deposition, likely due to a reduction in plasma HDL, an increased saturation of cholesteryl esters in apoB lipoproteins and, in the apoE-/- background, an increased plasma concentration of apoB lipoproteins.     

Does a HDL injection reduce the development of serum hyperlipidemia and progression of fatty streaks in cholesterol fed rabbits?

The influences of homologous (rabbit) or heterologous (human) high density lipoprotein (HDL) on the development of serum hyperlipidemia and progression of fatty streaks were studied in cholesterol fed rabbits. Three groups of New Zealand rabbits were fed a 0.5% cholesterol rich diet for 8 weeks. Additionally into these animals the following solutions were injected intravenously two times per week: group 1 (control): saline; group 2: human HDL dissolved in saline; group 3: rabbit HDL dissolved in saline. The animals of group 2 had lower serum cholesterol levels during the dietary period than rabbits of group 1 (p < 0.05) but the surface of intima covered with fatty streaks was the same as in group 1. On the other hand, the serum cholesterol level in rabbits of group 3 was the same as in group 1 during the whole experimental period, but the surface of aorta covered with fatty streaks was significantly lower (p < 0.05) in group 3 than in group 1. The results of this study support the hypothesis of an antiatherogenic action of HDL, which seems to be independent of the influence of HDL on the serum lipids but depends on the source of HDL.     

Effects of mild physical exercise on serum lipoproteins and metabolites of arachidonic acid: a controlled randomised trial in middle aged men.

To study the effects of physical exercise on biochemical risk factors for ischaemic heart disease 31 healthy middle aged men undertook regular physical exercise for two months and 29 served as controls in a randomised trial. In the men taking regular exercise serum cholesterol concentrations increased 26% more in the high density lipoprotein subfraction two (HDL2) and decreased 31% more in the subfraction three (HDL3) and 9% more in the low density lipoprotein fraction than in the control group. A tendency towards increased plasma 6-keto-prostaglandin F1 alpha concentration and decreased serum thromboxane B2 concentration was found during the period of regular exercise, but prostaglandin E2 concentrations remained unchanged. The increase in plasma 6-keto-prostaglandin F1 alpha concentration was associated with an increase in serum HDL2 cholesterol concentration in the group taking regular exercise. Our data suggest that mild regular physical exercise favourably influences cholesterol distribution in serum lipoproteins in healthy middle aged men and may have beneficial effects on circulating metabolites of arachidonic acid.     

高脂饮食豚鼠高密度脂蛋白代谢的特点

目的研究豚鼠高脂饮食后高密度脂蛋白代谢的特点,并与大鼠进行比较。方法将豚鼠和大鼠分别随机分为正常组（NC）和高脂组（HF）,正常组均给予普通饲料,高脂组给予高脂饲料诱导10周后,测定血清LDL-C、HDL-C水平,HDL3/HDL2比值和LCAT、CETP的表达;采用real-time RT-PCR方法检测肝脏SR-BI表达的变化。结果与正常组相比,豚鼠高脂组血清HDL-C水平显著升高,高密度脂蛋白亚型HDL3/HDL2的比值升高,血清CETP表达均显著增加,血清LCAT表达下降,肝脏SR-BI mRNA表达水平是正常组的2.27倍。而相同高脂饲料条件下,大鼠的上述指标均无明显变化。结论豚鼠摄入高脂饮食后HDL代谢与大鼠有所不同,主要表现为血清HDL-C升高,肝脏SR-BI受体表达增加,高密度脂蛋白亚型组分发生变化,大颗粒HDL2含量相对减少,小颗粒HDL3堆积,其机制与血清CETP、LCAT的变化密切相关。     

Effects of high sucrose diets and 4-aminopyrazolopyrimidine on serum lipids and lipoproteins in the rat

The effect of feeding a semipurified diet high in sucrose on serum lipid and lipoprotein concentrations was studied. In rats fed this diet the serum triglyceride concentration doubled, and liver triglyceride concentration increased by 30%. A fivefold increase in VLDL protein concentration and a small but significant increase of HDL protein concentration was also observed. In these rats there was increased incorporation of labeled amino acids into the proteins of plasma VLDL and HDL. Fatty livers developed in the animals receiving 4-aminopyrazolopyrimidine, and levels of serum triglyceride and cholesterol fell markedly. The concentration of all lipoprotein classes decreased, with VLDL showing the most marked effect. Incorporation of labeled amino acids into lipoproteins and other plasma proteins was depressed.     

Effects of the acute phase response on the concentration and density distribution of plasma lipids and apolipoproteins

Longitudinal studies were carried out in the rabbit model to determine alterations in the concentration and density distribution of plasma lipids and apolipoproteins during the acute phase response (APR) characterized by elevated levels of C-reactive protein (CRP) and serum amyloid A (SAA). Twelve hr after the intramuscular injection of croton oil, SAA was detectable in high density lipoprotein (HDL). At the height of the response (72 hr), HDL decreased while SAA became the major HDL apoprotein, up to 80% of the proteins in the higher density fractions. The SAA-enriched particles became denser (density of HDL3) but larger (size of HDL2), had slower electrophoretic mobility, and were depleted in apoA-I, cholesterol, triglyceride, and phospholipid. HDL-cholesterol decreased and was redistributed to other fractions while apoA-I disappeared from the circulation. During this time plasma triglycerides increased 6- to 10-fold while plasma cholesterol and phospholipids showed minimal changes. ApoB increased 5- to 6-fold while the apoB-containing particles shifted to higher density resulting in elevated IDL and then LDL during recovery. VLDL (d less than 1.006 g/ml) increased and acquired 30-40% of the plasma triglycerides, cholesterol, phospholipid, and apoB. SAA also increased in VLDL while apoE decreased.     

Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol.

Plasma cholesteryl esters, synthesized within high density lipoproteins (HDL), may be transferred from HDL particles to other lipoproteins by plasma cholesteryl ester transfer protein (CETP). Alcohol consumption is associated with increased HDL cholesterol concentration and reduced plasma CETP activity. The alcohol-induced decrease in CETP activity may be due to a low concentration of CETP in plasma or the inhibition of CETP by specific inhibitor proteins or alterations in the composition of plasma lipoproteins. The first two possibilities are studied further in this paper using data on 47 alcohol abusers and 31 control subjects. The activity of CETP was measured as the rate of cholesteryl ester transfer between radio-labeled low density lipoproteins and unlabeled HDL using an in vitro method independent of endogenous plasma lipoproteins. Plasma CETP concentration was determined by a Triton-based radioimmunoassay. The alcohol abusers consuming alcohol (on average 154 g/day) had 28% higher HDL cholesterol (P less than 0.01), 27% lower plasma CETP concentration (P less than 0.001), and 22% lower plasma CETP activity (P less than 0.001) than the controls. Plasma CETP concentration showed a negative correlation with HDL cholesterol among all the subjects (r = -0.317, P less than 0.01) but not among the alcohol abusers alone (r = -0.102, N. S.). During 2 weeks of alcohol withdrawal, plasma CETP concentration and activity of 8 subjects increased, whereas HDL cholesterol decreased by 42% (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of skim milk, skim milk yogurt, orotic acid, and uric acid on lipid metabolism in rats

The effects of feeding two milk products (skim milk and skim milk yogurt) and two proposed hypocholesterolemic factors (orotic acid and uric acid) on serum cholesterol (HDL, LDL, total, HDL/Total and HDL/LDL), liver lipids (total liver lipids and liver cholesterol), and aortal cholesterol were studied. Ten groups, of nine rats each, were fed isocaloric Chow-based diets containing water, 45% skim milk (SM), 45% skim milk yogurt (SMY), and 0.0025% orotic acid (OA) or 0.001% uric acid (UA), without or with cholesterol. The SM diet (with cholesterol) resulted not only in lower total cholesterol (P < 0.10), LDL cholesterol (P < 0.05), aortal cholesterol (P < 0.01), and liver cholesterol (P < 0.10), but also in increased HDL (P < 0.05) and HDL/LDL (P < 0.10) cholesterol ratio. The SMY diet, on the other hand, resulted in lowered total serum cholesterol (P < 0.05) and aortal cholesterol (P < 0.01) and in higher LDL (P < 0.05) cholesterol. The hypocholesterolemic effects were more marked for SM than for SMY. Addition of OA and UA to diets increased serum cholesterol, LDL cholesterol, and total liver lipids; the OA diet also increased liver cholesterol. Neither OA nor UA alone was the factor responsible for the hypocholesterolemic effects seen with SM and SMY feeding.     

Distribution of cholesterol and apolipoprotein A-I and A-II in human high density lipoprotein subfractions separated by CsCl equilibrium gradient centrifugation: evidence for HDL subpopulations with differing A-I/A-II molar ratios.

The purpose of this experiment was to characterize the high density lipoproteins (HDL) as a function of hydrated density. HDL was subfractionated on the basis of hydrated density by CsCl density gradient centrifugation of whole serum or the d 1.063-1.25 g/ml HDL fraction isolated from three men and three women. Apolipoprotein A-I and A-II quantitation by radial immunodiffusion showed that the A-I/A-II ratio varied with the lipoprotein hydrated density. The A-I/A-II molar ratio of HDL lipoproteins banding between d 1.106 and 1.150 g/ml was nearly constant at 2.2 +/- 0.2. In the density range 1.151-1.25 g/ml the A-I/A-II ratio increased as the density increased. On the other hand, in the density range between 1.077 and 1.105 the A-I/A-II ratio increased as the density decreased, ranging from 2.8 +/- 0.5 for the d 1.093-1.105 g/ml fraction to 5.6 +/- 1.3 for the d 1.077-1.082 g/ml fraction. The d 1.063-1.076 g/ml fraction and the d 1.077-1.082 g/ml fractions had comparable A-I/A-II ratios. Serum and the d 1.063-1.25 g/ml HDL fraction exhibited similar trends. The cholesterol/(A-I + A-II) ratio decreased as the density increased in all 12 samples (six serum and six HDL) examined. Gradient gel electrophoresis of the density gradient fractions showed that as the density increased from 1.063 to 1.200 g/ml the apparent molecular weight decreased from 3.9 x 10(5) to 1.1 x 10(5). HDL subfractions with the same hydrated densities had comparable molecular weights and A-I/A-II and cholesterol/(A-I + A-II) ratios when isolated from men or women. HDL contains subpopulations that differ in the A-I/A-II molar ratio.-Cheung, M. C., and J. J. Albers. Distribution of cholesterol and apolipoprotein A-I and A-II in human high density lipoprotein subfractions separated by CsCl equilibrium gradient centrifugation: evidence for HDL subpopulations with differing A-I/A-II molar ratios.     

Effects of fasting on serum lipids and lipoprotein profiles in the egg-laying hen (Gallus domesticus)

The effects of a 24-h fast on serum lipids and lipoprotein profiles in commercial laying hens were investigated. Blood was analyzed at 34 and 46 weeks of age from Single Comb White Leghorn hens that had been either fed ad libitum or had been fasted for 24 h prior to collection. At 12 weeks, birds were divided into 16 biological isolation units, with 8 replicate units assigned to each treatment group. Four birds out of 10 in each unit were tagged for bleeding. Parameters evaluated included total serum cholesterol and triglycerides, mean diameters of very low density lipoproteins (VLDLs) for the 10th, 50th, and 90th percentiles of serum total VLDL, mean total population VLDL particle diameter (MPD), and percentage serum cholesterol recovered in VLDL, low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions. Fasting led to decreases in total serum cholesterol and triglycerides, and a decrease in mean serum VLDL particle diameter in the 90th population percentile. At Week 34, percentage serum cholesterol recovered from LDL was increased, whereas percentage serum cholesterol recovered from HDL was decreased due to fasting. At Week 46, MPD and percentage serum cholesterol recovered from VLDL were decreased, whereas percentage serum cholesterol recovered from HDL was increased due to fasting. It was concluded that a 24-h fast decreased serum lipids (cholesterol and triglycerides) and the size of VLDL particles in the 90th population percentile in commercial laying hens. Furthermore, bird age influenced the effects of a 24-h fast on MPD and the redistribution of serum cholesterol among VLDL, LDL, and HDL particles.     

Effects of dietary fish oil on plasma high density lipoprotein. Electron spin resonance and fluorescence polarization studies of lipid ordering and dynamics.

Dietary fish oils are implicated in reducing the incidence of coronary heart disease, perhaps by altering the properties of plasma lipoproteins. The hypothesis that omega-3 polyunsaturated fatty acids (PUFA) in fish oils produce changes in lipid ordering and dynamics within high density lipoprotein (HDL), thereby potentially modifying cholesterol transport, is investigated here. Rabbits were fed a diet supplemented with either 10% (by weight) menhaden oil (MO), a fish oil rich in omega-3 PUFAs, or hydrogenated cottonseed oil for a period of 12 weeks. HDL was isolated by sequential flotation ultracentrifugation from plasma drawn every 2 weeks. Gas chromatography confirmed that the predominant omega-3 PUFAs of fish oils, eicosapentaenoic 20:5 and docosahexaenoic 22:6 acids, were only incorporated into the triglyceride, phospholipid, and cholesteryl ester constituents of lipoproteins from rabbits on the MO diet. ESR of 5- and 16-doxyl stearic acids demonstrates that molecular order and dynamics within the outer monolayer of HDL is virtually unaffected. In contrast, ESR of cholesteryl 12-doxyl stearate indicates order is less within the inner apolar core of the lipoprotein for the MO diet than for the hydrogenated cottonseed oil diet. Fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene supports this finding. The greater disorder detected within HDL from rabbits fed fish oil may result in an enhancement of cholesterol exchange between lipoproteins and between lipoproteins and cells, which may have anti-atherogenic ramifications.     

Effect of dietary fiber of “Rihane” barley grains and azoxymethane on serum and liver lipid variables in Wistar rats

The aim of the present study is to evaluate the effects of diet enriched with dietary fiber of barley variety “Rihane” and azoxymethane on serum and liver lipid variables in male rats. Forty male rats were divided into four groups and fed on control diet or experimental diet that contained control enriched with dietary fiber of barley variety “Rihane”. Animals were injected with saline (controls) or azoxymethane (20 mg/kg body weight s.c.) at 7 and 8 weeks of age. The experimental diet significantly decreased cholesterol level compared with the control diet. Rats fed with BR diet significantly increased the serum high-density lipoprotein (HDL) cholesterol and significantly decreased low-density lipoprotein (LDL) cholesterol concentrations. The experimental diet decreased the atherogenic index (p < 0.05) compared with the control diet. Whereas the azoxymethane induced a significant increase of liver lipid, serum LDL and triglyceride concentrations, but it caused a significant reduction of HDL. Consequently, the ratio of HDL/TC decreased significantly compared with the control (p < 0.05). Accordingly, these results indicated that the diet enriched with dietary fiber of barley variety “Rihane” could be effective in decreasing the atherogenic risk factors in rats whereas the use of the azoxymethane as colon-specific carcinogen substance altered the lipid metabolism.     

Hyperlipidemia-Associated Renal Damage Decreases Klotho Expression in Kidneys from ApoE Knockout Mice

Background

Klotho is a renal protein with anti-aging properties that is downregulated in conditions related to kidney injury. Hyperlipidemia accelerates the progression of renal damage, but the mechanisms of the deleterious effects of hyperlipidemia remain unclear.

Methods

We evaluated whether hyperlipidemia modulates Klotho expression in kidneys from C57BL/6 and hyperlipidemic apolipoprotein E knockout (ApoE KO) mice fed with a normal chow diet (ND) or a Western-type high cholesterol-fat diet (HC) for 5 to 10 weeks, respectively.

Results

In ApoE KO mice, the HC diet increased serum and renal cholesterol levels, kidney injury severity, kidney macrophage infiltration and inflammatory chemokine expression. A significant reduction in Klotho mRNA and protein expression was observed in kidneys from hypercholesteromic ApoE KO mice fed a HC diet as compared with controls, both at 5 and 10 weeks. In order to study the mechanism involved in Klotho down-regulation, murine tubular epithelial cells were treated with ox-LDL. Oxidized-LDL were effectively uptaken by tubular cells and decreased both Klotho mRNA and protein expression in a time- and dose-dependent manner in these cells. Finally, NF-κB and ERK inhibitors prevented ox-LDL-induced Klotho downregulation.

Conclusion

Our results suggest that hyperlipidemia-associated kidney injury decreases renal expression of Klotho. Therefore, Klotho could be a key element explaining the relationship between hyperlipidemia and aging with renal disease.     

Incorporation of excess cholesterol by high density serum lipoproteins.

Excess cholesterol was added to human HDL3 and to bovine mammalian high density serum lipoprotein (HDL) by incubating aqueous lipoprotein solutions with solid dispersions of [4-(14)C]cholesterol on Celite. Lipoprotein cholesterol complexes were isolated by centrifugation and filtration through a Sepharose 4B column. The pure complexes were analyzed for protein and lipid content and composition and were subsequently investigated by physical methods (analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy), in order to detect any structural changes induced by added cholesterol. The rates of cholesterol uptake varied as an inverse function of the intrinsic cholesterol present in the native lipoproteins. The maximum cholesterol taken up by human HDL3 increased the free cholesterol content from 3--4% (initial) up to 22% of the total lipoprotein weight. Bovine HDL was observed to increase its free cholesterol content from 2--4% (initial) up to 11--17% of the total lipoprotein weight, before denaturation. At maximum levels of added cholesterol, both lipoproteins had increased molecular weights and sedimentation velocity coefficients corresponding to the increased mass of the particles. No major changes in the hydrodynamic properties were observed. At the molecular level, the protein components only showed a 15--20% decrease in fluorescence intensity, possibly a consequence of a modified environment of the aromatic amino acid residues. In the human HDL3, added cholesterol increased the microviscosity of the lipid domains by 1.2 P at 25 degrees C (from 3.4 to 4.6 P), but did not affect the fluidity of bovine HDL lipids (5.9 P).