The effect of Puerariae radix on lipoprotein metabolism in liver and intestinal cells

BACKGROUND: Animal studies investigating the beneficial effects of Puerariae radix on cardiovascular disease have suggested this plant possesses anti-diabetic and lipid lowering properties. However, the exact mechanism by which Puerariae radix affects lipid metabolism is currently unknown. The aim of this study was to investigate the effect of the water extract of Puerariae radix on the secretion of VLDL and chylomicrons from HepG2 liver cells and CaCo2 cells, respectively, in humans. METHODS: The amount of apoB(100 )(a protein marker for VLDL) and apoB(48 )(a protein marker for chylomicrons) in cells and media were quantified by Western Blotting and enhanced chemiluminescence (ECL). Total, free and esterified cholesterol concentrations were measured by gas liquid chromatography. RESULTS: Treatment of cells with water extract of Puerariae radix significantly decreased apoB(100 )production and secretion from HepG2 cells up to 66% in a dose dependent manner. The intracellular total cholesterol and free cholesterol concentration in HepG2 cells also decreased with increasing concentration of the Puerariae radix. In contrast, water extract of Puerariae radix attenuated apoB(48 )concentrations in cells, but not apoB(48 )secretion from CaCo2 enterocytes. CONCLUSIONS: Collectively, our findings suggest that the water extract of Puerariae radix attenuates the hepatic lipoprotein production and secretion. Our present cell culture findings may explain why circulating VLDL and LDL levels were attenuated in animals supplemented with Puerariae radix. Since decreasing the production and secretion of atherogenic lipoproteins decreases the risk of development of cardiovascular disease, diets supplemented with radix may provide a safe and effective beneficial cardioprotective effects in humans

Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women

Role of Heparanase on Hepatic Uptake of Intestinal Derived Lipoprotein and Fatty Streak Formation in Mice

BACKGROUND: Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. PRINCIPAL FINDINGS: To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm(2)±5,922 vs. 4,189 µm(2)±1,130, p<0.001). CONCLUSIONS: Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks

Intrapopulation Variability Shaping Isotope Discrimination and Turnover: Experimental Evidence in Arctic Foxes

Tissue-specific stable isotope signatures can provide insights into the trophic ecology of consumers and their roles in food webs. Two parameters are central for making valid inferences based on stable isotopes, isotopic discrimination (difference in isotopic ratio between consumer and its diet) and turnover time (renewal process of molecules in a given tissue usually measured when half of the tissue composition has changed). We investigated simultaneously the effects of age, sex, and diet types on the variation of discrimination and half-life in nitrogen and carbon stable isotopes (δ15N and δ13C, respectively) in five tissues (blood cells, plasma, muscle, liver, nail, and hair) of a top predator, the arctic fox Vulpes lagopus. We fed 40 farmed foxes (equal numbers of adults and yearlings of both sexes) with diet capturing the range of resources used by their wild counterparts. We found that, for a single species, six tissues, and three diet types, the range of discrimination values can be almost as large as what is known at the scale of the whole mammalian or avian class. Discrimination varied depending on sex, age, tissue, and diet types, ranging from 0.3‰ to 5.3‰ (mean = 2.6‰) for δ15N and from 0.2‰ to 2.9‰ (mean = 0.9‰) for δ13C. We also found an impact of population structure on δ15N half-life in blood cells. Varying across individuals, δ15N half-life in plasma (6 to 10 days) was also shorter than for δ13C (14 to 22 days), though δ15N and δ13C half-lives are usually considered as equal. Overall, our multi-factorial experiment revealed that at least six levels of isotopic variations could co-occur in the same population. Our experimental analysis provides a framework for quantifying multiple sources of variation in isotopic discrimination and half-life that needs to be taken into account when designing and analysing ecological field studies

Ape parasite origins of human malaria virulence genes

Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum

Women experience lower postprandial oxidative stress compared to men

BACKGROUND: Women have enhanced triglyceride (TAG) removal from the circulation following consumption of high-fat loads, potentially leading to decreased reactive oxygen and nitrogen species (RONS) generation. This may have implications related to long-term health outcomes. We examined the oxidative stress response to high-fat feeding between men and women to determine if women are less prone to postprandial oxidative stress as compared to men. METHODS: A total of 49 women (mean age: 31 ± 12 yrs) and 49 men (mean age: 27 ± 9 yrs) consumed a high-fat meal in the morning hours following a 10–12 hour overnight fast. Blood samples were collected before and at 2 and 4 hours after the meal. Samples were analyzed for TAG, various markers of oxidative stress (malondialdehyde [MDA], hydrogen peroxide [H(2)O(2)], Advanced Oxidation Protein Products [AOPP], nitrate/nitrite [NOx]), and Trolox-Equivalent Antioxidant Capacity (TEAC). Area under the curve (AUC) was calculated for each variable. Effect size calculations were performed using Cohen’s d. Data from the total sample of 98 subjects were collected as a part of six previously conducted studies in our lab focused on postprandial oxidative stress, between 2007 and 2012. RESULTS: AUC was higher for men compared to women for TAG (249.0 ± 21.5 vs. 145.0 ± 9.8 mg·dL(-1)·4 hr(-1); p < 0.0001; effect size = 0.89), MDA (2.7 ± 0.2 vs. 2.2 ± 0.1 μmol·L(-1)·4 hr(-1); p = 0.009; effect size = 0.47), H(2)O(2) (29.9 ± 2.4 vs. 22.5 ± 1.6 μmol·L(-1)·4 hr(-1); p = 0.001; effect size = 0.55), AOPP (92.8 ± 6.9 vs. 56.4 ± 3.7 μmol·L(-1)·4 hr(-1); p < 0.0001; effect size = 1.38), and TEAC (1.7 ± 0.1 vs. 1.3 ± 0.0 mmol·L(-1)·4 hr(-1); p = 0.002; effect size = 0.91). No significant difference was noted for NOx (42.2 ± 4.6 vs. 38.3 ± 3.5 μmol·L(-1)·4 hr(-1) for men and women, respectively; p = 0.09; effect size = 0.17). CONCLUSION: In the context of the current design, women experienced lower postprandial oxidative stress compared to men. Future work is needed to determine the potential health implications of lower postprandial oxidative stress in women