Affect Plasma Total Cholesterol Research Articles

Synthesis of cholesterol analogues and comparison on their effect on plasma cholesterol with β-Sitosterol

The application of plant sterols in the treatment of hypercholesterolemia is promising. We hypothesize that plant sterols can reduce blood cholesterol because they have a side chain of at least three branches. Three cholesterol analogues were synthesized: CA0 (no side chain), CA3 (a 3‑carbon chain with one branch), and CA14 (a 14‑carbon side chain with two branches), and then compared their effect on blood cholesterol with that of β-sitosterol. Structurally, β-sitosterol has a 10‑carbon side chain with three branches. Results demonstrated that β-sitosterol could effectively reduce plasma total cholesterol (TC) by 20.3%, whereas CA0, CA3 and CA14 did not affect plasma TC in hypercholesterolemia hamsters. β-Sitosterol was absent in the plasma and liver, indicating it was not absorbed. We concluded that β-sitosterol with three branches had plasma TC-lowering activity. In contrast, cholesterol analogues with a side chain of two or fewer branches did not affect plasma cholesterol.

Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosisviagut microbiota

BACKGROUNDObesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.AIMTo investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.METHODSWe extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.RESULTSWe found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 ± 1.02 vs 40.53 ± 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.CONCLUSIONOur study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.

Dietary Cholesterol Contained in Whole Eggs Is Not Well Absorbed and Does Not Acutely Affect Plasma Total Cholesterol Concentration in Men and Women: Results from 2 Randomized Controlled Crossover Studies.

Whole egg is a food source of dietary cholesterol and inconsistent research findings exist about the effect of dietary cholesterol from whole egg on blood cholesterol concentration. We assessed the effect of co-consuming cooked whole egg (CWE) on dietary cholesterol absorption from two randomized-crossover studies. For study 1, 16 men consumed raw vegetables with no egg, 75 g CWE, or 150 g CWE. For study 2, 17 women consumed cooked vegetables with no egg or 100 g CWE. Triacylglycerol-rich lipoprotein fractions (TRL) were isolated from collected blood. In study 1, total-cholesterol areas under the curve (AUC)0–10h in TRL were not different but triacylglycerol AUC0–10h in TRL was greater for 150 g CWE vs. 75 g CWE and no egg. Similarly, in study 2, total-cholesterol AUC0–10h in TRL was not different but triacylglycerol AUC0–10h in TRL was greater for 100 g CWE vs. no egg. In both studies, whole egg consumption did not affect plasma total-cholesterol AUC0–10h, while triacylglycerol AUC0–10h was increased. These results suggest that the dietary cholesterol in whole egg was not well absorbed, which may provide mechanistic insight for why it does not acutely influence plasma total-cholesterol concentration and is not associated with longer-term plasma cholesterol control.

Dietary Cholesterol Contained in Whole Eggs is Not Well Absorbed and Does Not Affect Plasma Total Cholesterol Concentration in Men and Women: Results from Two Randomized Controlled Crossover Trials

Whole egg is a well‐known food source of dietary cholesterol and inconsistent research findings exist about the effect of dietary cholesterol from whole egg on blood cholesterol concentration. A previous animal study reported that phosphatidylcholine in egg yolk inhibits dietary cholesterol uptake by the intestine. Therefore, in this study, we assessed the effect of co‐consuming cooked whole eggs on dietary cholesterol absorption in adults from 2 randomized controlled crossover trials.For study 1, 16 men (mean ± SE; age: 24 ± 1 y; BMI: 24 ± 1 kg/m2) consumed a raw mixed vegetable salad (0 mg dietary cholesterol) with no egg, with 75 g cooked whole egg (CWE) (280 mg dietary cholesterol), or with 150 g CWE (560 mg dietary cholesterol). For study 2, 17 women (age: 45 ± 4 y; BMI: 25 ± 2 kg/m2) consumed cooked mixed vegetables (0 mg dietary cholesterol) with no egg or with 100 g CWE (373 mg dietary cholesterol). In both studies, blood was collected hourly for 10 hours and triacylglycerol‐rich lipoprotein (TRL) fractions were isolated. Total cholesterol and triacylglycerol concentrations in TRL fractions and plasma were analyzed and composite areas under the curve (AUCs) were calculated. Concentrations of total cholesterol and triacylglycerol within TRL fractions represent newly absorbed cholesterol and triacylglycerol.In study 1, total cholesterol AUC0–10h in TRL fractions was not different among 150 g CWE vs. 75 g CWE vs. no egg (lsmean ± SE; 5.3 ± 1.2 vs. 4.2 ± 1.2 vs. 1.7 ± 1.2 mg • dL−1 • 10h, p = 0.11) but triacylglycerol AUC0–10h in TRL fractions was greater for 150 g CWE vs. 75 g CWE and no egg (79 ± 12a vs. 21 ± 12b vs. 13 ± 12b mg • dL−1 • 10h, p = 0.0005). Similarly, in study 2, total cholesterol AUC0–10h in TRL fractions was not different between 100 g CWE vs. no egg (5.2 ± 0.9 vs. 3.8 ± 0.9 mg • dL−1 • 10h, p = 0.30) but triacylglycerol AUC0–10h in TRL fractions was greater for 100 g CWE vs. no egg (31 ± 3a vs. 11 ± 3b mg • dL−1 • 10h, p &lt; 0.0001). In both studies, plasma total cholesterol AUC0–10h was not affected by egg consumption (23 ± 13 vs. 20 ± 13 vs. 22 ± 13 mg • dL−1 • 10h, p = 0.92; 50 ± 11 vs. 43 ± 11 mg • dL−1 • 10h, p = 0.65), while triacylglycerol AUC0–10h was increased (207 ± 36 vs. 66 ± 36 vs. 66 ± 36 mg • dL−1 • 10h, p = 0.0097; 125 ± 23 vs. 50 ± 23 mg • dL−1 • 10h, p = 0.0257) when subjects consumed more eggs that contain greater amounts of dietary cholesterol and triacylglycerol.Collectively, these findings support that the dietary cholesterol found in whole eggs was not well absorbed and did not affect plasma total cholesterol concentration, although whole egg contains high amount of dietary cholesterol. Thus, increased intake of dietary cholesterol from eggs may not indeed raise the blood cholesterol concentration.Support or Funding InformationSupport: American Egg Board‐Egg Nutrition Center; NIH UL1TR001108; Purdue Ingestive Behavior Research Center

Contrast ultrasound imaging of the aorta does not affect progression of atherosclerosis in ApoE−/− mice

Ultrasound Contrast Agents (UCAs) are used clinically to enhance ultrasound imaging of the cardiovascular system. Adverse biological effects have been noted after administration of UCAs, and more research is needed for an understanding of the biological effects of UCAs. Male ApoE−/− mice (8 weeks old, n=38) were intravenously infused with the Definity® UCA (2×1010 UCA/hr) and either exposed to 2.8‐MHz 10‐Hz PRF 1.4‐μs PD 2‐min ED 1.4‐MPa PRPA ultrasound or sham exposed, and then consumed either a chow or Western diet for either 4 or 8 weeks after ultrasound exposure (n=4–5 per group). Plasma total cholesterol was greater in the Western diet group than the chow group for all timepoints after baseline (p&lt;0.0001). Plasma von Willebrand Factor (vWF), a biomarker of endothelial function, was elevated in Western diet animals compared to chow animals (p&lt;0.05). Atheroma thickness was greater in animals consuming the Western diet than in chow‐fed animals (p&lt;0.001), and in animals euthanized after 8 weeks than after 4 weeks (p&lt;0.005). Ultrasound did not affect plasma total cholesterol levels, plasma vWF or atheroma thickness. [Supported by NIH R37EB002641]

Ritonavir protects against the development of atherosclerosis in APOE*3-Leiden mice

ObjectiveThe use of the HIV-protease inhibitor ritonavir (RTV) is associated with induction of hypertriglyceridemia, which is a cardiovascular risk factor. Therefore, we investigated the effect of RTV on atherosclerosis development in APOE*3-Leiden transgenic mice, a model for human-like lipoprotein metabolism and atherosclerosis. Methods and resultsAPOE*3-Leiden mice were fed a Western-type diet without or with RTV (35mg/kg/day) for 19 weeks. RTV increased plasma TG levels throughout the study (∼2-fold; P<0.05). Despite these increased TG levels, RTV decreased the atherosclerotic lesion area in the aortic root (−57%; P<0.05), concomitant with reduced macrophage area (−72%; P<0.01) and decreased lesion severity. This could not be explained by reduced inflammatory markers in plasma (i.e. serum amyloid A, E-selectin and fibrinogen), nor by decreased lipid accumulation in macrophages or increased cholesterol efflux from macrophages, as assessed using peritoneal macrophages in vitro. Rather, whereas RTV did not affect plasma total cholesterol levels, RTV decreased (V)LDL-cholesterol and increased cholesterol in apoE-rich large HDL. ConclusionDespite inducing hypertriglyceridemia, RTV decreases atherosclerotic lesion area and severity, associated with decreased (V)LDL-cholesterol and increased atheroprotective apoE-rich large HDL.

Apple polyphenols inhibit plasma CETP activity and reduce the ratio of non‐HDL to HDL cholesterol

Previous reports demonstrated that hypocholesterolemic activity of apple was associated with its pectin and fiber. This report was to investigate the effect of apple polyphenols (AP) on blood cholesterol level and gene expression of cholesterol-regulating enzymes in Golden Syrian hamsters maintained on a 0.1% cholesterol diet. It was found that dietary supplementation of 0.3 or 0.6% of AP did not affect plasma total cholesterol (TC), but it increased HDL cholesterol (HDL-C) and decreased non-HDL-C, thus leading to a lower ratio of non-HDL-C to HDL-C. Plasma total triacylglycerol (TG) level was also significantly reduced when hamsters were fed a diet supplemented with 0.6% AP. Western blot analysis did not find any effect of AP on sterol regulatory element-binding protein 2 (SREBP-2), LDL receptor (LDLR), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and cholesterol-7alpha-hydroxylase (CYP7A). Most interesting was that supplementation of AP had no effect on protein abundance of plasma cholesteryl ester transport protein (CETP), but it suppressed plasma CETP activity. A series of in vitro assays confirmed that AP inhibited CETP in a dose dependent manner. It was concluded that AP favorably improved distribution of cholesterol in lipoproteins, most likely, by its inhibition on CETP activity.

VLDL Metabolism in Rats Is Affected by the Concentration and Source of Dietary Protein

The present study was designed to determine if changes in dietary protein level and source are related to changes in VLDL lipid concentrations and VLDL binding by hepatic membranes and isolated hepatocytes. Male Wistar rats were fed cholesterol-free diets containing 10, 20 or 30 g/100 g casein or highly purified soybean protein for 4 wk. Hepatic, plasma and VLDL lipids, VLDL apo B-100 and VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane were determined. Increasing casein or soybean protein level (from 10 to 30 g/100 g) in the diet increased VLDL apo B-100, indicating an increase in the number of VLDL particles. VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane increased when the protein level increased from 10 to 20 g/100 g in the diet and decreased with 30 g/100 g protein, regardless of protein type. The dietary protein source did not affect plasma total cholesterol concentrations at any protein level. Feeding 20 g/100 g soybean protein compared with casein lowered plasma triglyceride concentrations and VLDL number as measured by decreased VLDL-protein, -phospholipid, -triglyceride, -cholesterol and -apo B-100. VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane were higher in rats fed soybean protein than those fed casein. The higher VLDL uptake could be responsible for the hypotriglyceridemia in rats fed soybean protein.

The Effects of Polyunsaturated Fat vs Monounsaturated Fat on Plasma Lipoproteins: The Power of a Study

To the Editor.— It is amazing that despite all the attempts over the past few years to increase the appropriate use of statistics in the general medical literature, you have once again published an interventional trial with negative results with no discussion whatever of the power of the study to detect a difference in the study groups. 1 following statement by Dreon et al 1 is simply false: The present results in free-living men and women demonstrated that exchanging unsaturated fats within current guidelines in reduced- fat diets does not affect plasma total cholesterol or LDL [low-density lipoprotein] cholesterol levels. What is true is that the study failed to demonstrate an effect of exchanging unsaturated fats, but the authors do not discuss what the chance is that this was simply because the study groups were too small. I grant you that they did make one insufficient allusion to wide

Effect of different types of dietary fibre on plasma lipids

One way in which regular consumption of dietary fibre could be related to the eventual development of coronary and other atherosclerotic disease is via the plasma·total or low-density lipoprotein cholesterol. Short-term human experiments under a variety of conditions have shown that wheat fibre does not affect plasma total cholesterol. However pectin and guar gum lower plasma cholesterol in man. Other viscous types of ‘dietary fibre’ and vegetable foods rich in pectin would repay similar investigation. There is clearly a dissociation between the effects of different types of dietary fibre on plasma lipids and on colonic function.