Dietary phospholipids, hepatic lipid metabolism and cardiovascular disease

PURPOSE OF REVIEW: An increasing number of studies in experimental animals suggest that dietary phospholipids might be of benefit in the treatment of fatty liver disease. This raises the possibility that synthetic or naturally occurring phospholipid isolates could be used as hepatoprotective nutraceuticals or functional foods. The aim of the present article is to review published data describing the beneficial effects of dietary phospholipids on hepatic lipid metabolism and their potential to affect atherosclerosis and cardiovascular disease. RECENT FINDINGS: Consistent results have been obtained supporting the concept that phospholipid from various sources (i.e., soybean, safflower, egg and fish roe) can reduce liver lipid levels. The primary site of action for this effect appears to be in the intestinal lumen, where dietary phospholipids are able to interfere with neutral sterol absorption. Results have also been obtained suggesting that dietary phospholipids can stimulate bile acid and cholesterol secretion. Additional work suggests that dietary phospholipids can have a beneficial effect on plasma lipid and lipoprotein levels. SUMMARY: The concept of using naturally occurring compounds such as phospholipid to treat or prevent hepatic steatosis is very attractive. Controlled human trials are, however, required to verify the efficacy of this approach. It is also important that additional research be conducted to determine the extent to which certain phospholipids have the ability to increase plasma HDL levels and potentially affect the onset or development of cardiovascular disease.     

Sex differences in lipid metabolism and metabolic disease risk

The ability of nutrients to regulate specific metabolic pathways is often overshadowed by their role in basic sustenance. Consequently, the mechanisms whereby these nutrients protect against or promote a variety of acquired metabolic syndromes remains poorly understood. Premenopausal women are generally protected from the adverse effects of obesity despite having a greater proportion of body fat than men. Menopause is often associated with a transformation in body fat morphology and a gradual increase in the susceptibility to metabolic complications, eventually reaching the point where women and men are at equal risk. These phenomena are not explained solely by changes in food preference or nutrient intake suggesting an important role for the sex hormones in regulating the metabolic fate of nutrients and protecting against metabolic disease pathophysiology. Here, we discuss how differences in the acquisition, trafficking, and subceullular metabolism of fats and other lipid soluble nutrients in major organ systems can create overt sex-specific phenotypes, modulate metabolic disease risk, and contribute to the rise in obesity in the modern sedentary climate. Identifying the molecular mechanisms underpinning sex differences in fat metabolism requires the unravelling of the interactions among sex chromosome effects, the hormonal milieu, and diet composition. Understanding the mechanisms that give rise to sex differences in metabolism will help to rationalize treatment strategies for the management of sex-specific metabolic disease risk factors.     

Dietary fiber, lipid metabolism, and atherosclerosis

Despite the physiochemical complexity of dietary fibers (plant cell walls) and their individual components, there is substantial epidemiologic, clinical, and experimental evidence that these dietary components may have a role in modifying certain risk factors in coronary heart disease. Particulate fibers, such as wheat bran, do not appear to significantly alter plasma lipids or lipoprotein distributions in humans, or the atherogenicity of diets in experimental animals. Dietary fibers found in fruits, legumes, and vegetables, in contrast, show more definitive responses. Among the fiber isolates, the gelling and mucilaginous fibers, such as pectins and guar gum, predictably decrease circulating lipids in humans and animals and increase excretion of fecal metabolites of cholesterol, the bile acids. These fibers and fiber components can be shown to influence luminal solubility of lipids and the extent of lymphatic absorption of both cholesterol and triglyceride. In addition, these same fibers are effective in reducing postprandial levels of glucose, insulin, and other hormones. These direct effects on lipid absorption, and secondary effects of glucose and insulin on hepatic and peripheral lipoprotein metabolism, can account for many of the hypolipidemic responses to specific dietary fibers or their components, and may be of long-term consequence in coronary heart disease.     

Ethnic differences in lipid metabolism in two groups of obese South African women

There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), all premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin lipoprotein lipase activity were measured during an oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW.These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition.     

Cytokines, macrophage lipid metabolism and foam cells: implications for cardiovascular disease therapy

Cardiovascular disease is the biggest killer globally and the principal contributing factor to the pathology is atherosclerosis; a chronic, inflammatory disorder characterized by lipid and cholesterol accumulation and the development of fibrotic plaques within the walls of large and medium arteries. Macrophages are fundamental to the immune response directed to the site of inflammation and their normal, protective function is harnessed, detrimentally, in atherosclerosis. Macrophages contribute to plaque development by internalizing native and modified lipoproteins to convert them into cholesterol-rich foam cells. Foam cells not only help to bridge the innate and adaptive immune response to atherosclerosis but also accumulate to create fatty streaks, which help shape the architecture of advanced plaques. Foam cell formation involves the disruption of normal macrophage cholesterol metabolism, which is governed by a homeostatic mechanism that controls the uptake, intracellular metabolism, and efflux of cholesterol. It has emerged over the last 20 years that an array of cytokines, including interferon-γ, transforming growth factor-β1, interleukin-1β, and interleukin-10, are able to manipulate these processes. Foam cell targeting, anti-inflammatory therapies, such as agonists of nuclear receptors and statins, are known to regulate the actions of pro- and anti-atherogenic cytokines indirectly of their primary pharmacological function. A clear understanding of macrophage foam cell biology will hopefully enable novel foam cell targeting therapies to be developed for use in the clinical intervention of atherosclerosis.     

Peroxisomes, lipid metabolism, and human disease

In the past few years, much has been learned about the metabolic functions of peroxisomes. These studies have shown that peroxisomes play a major role in lipid metabolism, including fatty acid β-oxidation, etherphospholipid biosynthesis, and phytanic acid α-oxidation. This article describes the current state of knowledge concerning the role of peroxisomes in these processes, especially in relation to various peroxisomal disorders in which there is an impairment in peroxisomal lipid metabolism.     

Ethnic disparities in estimated cardiovascular disease risk in Amsterdam,the Netherlands

Background

Ethnic differences have been reported in cardiovascular disease (CVD) risk factors. It is still unclear which ethnic groups are most at risk for CVD when all traditional CVD risk factors are considered together as overall risk.

Objectives

To examine ethnic differences in overall estimated CVD risk and the risk factors that contribute to these differences.

Design

Using data of the multi-ethnic HELIUS study (HEalthy LIfe in an Urban Setting) from Amsterdam, we examined whether estimated CVD risk and risk factors among those eligible for CVD risk estimation differed between participants of Dutch, South Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin. Using the Systematic COronary Risk Evaluation (SCORE) algorithm, we estimated risk of fatal CVD and risk of fatal plus non-fatal CVD. These risks were compared between ethnic groups via age-adjusted linear regression analyses.

Results

The SCORE algorithm was applicable to 9,128 participants. Relative to the fatal CVD risk of participants of Dutch origin, South Asian Surinamese participants showed a higher fatal CVD risk, Ghanaian males a lower fatal CVD risk, and participants of other ethnic origins a similar fatal CVD risk. For fatal plus non-fatal CVD risk, African Surinamese and Turkish men also showed a higher risk. When diabetes was incorporated in the CVD risk algorithm, all but Ghanaian men showed a higher CVD risk relative to the participants of Dutch origin (betas ranging from 0.98–3.10%). The CVD risk factors that contribute the most to these ethnic differences varied between ethnic groups.

Conclusion

Ethnic minority groups are at a greater estimated risk of fatal plus non-fatal CVD relative to the group of native Dutch. Further research is necessary to determine whether this will translate to ethnic differences in CVD incidence and, if so, whether ethnic-specific CVD prevention strategies are warranted.

     

Common carotid artery stiffness, cardiovascular function and lipid metabolism after menopause

While cardiovascular disease is a major cause of death in elderly women, relatively little is known regarding the influence of menopause on atherogenesis. We tried to characterize postmenopausal changes in the arterial properties. A group of 72 postmenopausal women were classified into subgroups based on duration of the postmenopausal period (PMP): Group PM1 (1-2 years; n = 16), PM4 (2-6 years; n = 16), PM8 (6-10 years; n = 25), and PM12 (10-15 years; n = 15). The control group consisted of 24 volunteers with regular menstruation (PM0). The diameter pulse waveform and intima-media thickness (IMT) of the common carotid artery (CCA) was measured using a phase-locked echo tracking system coupled with B-mode ultrasonography. The stiffness index was calculated from the waveform and the systemic blood pressure. The cardiac contractile force and the cerebral perfusion were also estimated using the maximum incremental velocity (MIV) and the calculated blood flow, as well as the fasting lipid profile. When compared to control, significant and progressive increases were noted in total cholesterol and low density lipoprotein (PM1, PM4, PM8, PM12), IMT (PM8, PM12), and SI (PM1, PM4, PM8, PM12). Further significant and progressive reductions were noted in pulse amplitude of CCA diameter (PM1, PM4, PM8, PM12) and MIV and cerebral perfusion (PM8, PM12). The postmenopausal increase in CCA stiffness as well as lipid profile occurs earlier than the increase in IMT and may be a more sensitive predictor of disorder on arterial property.     

Xinnaokang improves cecal microbiota and lipid metabolism to target atherosclerosis

This study aims to explore the potential mechanisms of Xinnaokang in atherosclerosis treatment. Firstly, the active components of Xinnaokang were analysed by HPLC, which contains ginsenoside Rg1, puerarin, tanshinone, notoginsenoside R1, ammonium glycyrrhizate and glycyrrhizin. Network pharmacology analysis showed there were 145 common targets of Xinnaokang, including the chemical stress, lipid metabolite, lipopolysaccharide, molecules of bacterial origin, nuclear receptor and fluid shear stress pathways. Then, the animal experiment showed that Xinnaokang reduced the body weight and blood lipid levels of atherosclerotic mice. Vascular plaque formation was increased in atherosclerotic mice, which was markedly reversed by Xinnaokang. In addition, Xinnaokang reduced CAV-1 expression and increased ABCA1, SREBP-1 and LXR expressions in the vasculature. Xinnaokang promoted SREBP-2 and LDLR expressions in the liver but decreased IDOL and PCSK9 expressions, indicating that Xinnaokang regulated lipid transport-related protein expression. Cecal microbiota diversity was reduced in atherosclerotic mice but increased after Xinnaokang treatment. Xinnaokang treatment also improved gut microbiota communities by enriching Actinobacteria, Bifidobacteriales and Bifidobacteriaceae abundances. Metabolic profile showed that Xinnaokang significantly reduced homogentisate, phenylacetylglycine, alanine and methionine expressions in the liver of atherosclerotic mice. Xinnaokang effectively alleviated atherosclerosis, and this effect might be linked with the altered features of the liver metabolite profiles and cecal microbiota.     

Postprandial lipoprotein metabolism, genes and risk of cardiovascular disease

PURPOSE OF REVIEW: Several lines of evidence suggest that postprandial lipemia increases the risk of atherogenesis, and in each of the systems involved in postprandial metabolism the roles of many genes have been explored in order to establish the possible implications of their variability in coronary heart disease risk. RECENT FINDINGS: This report focuses on recent results pertaining to postprandial lipoprotein metabolism and genes, their variability and their relationship with intermediate phenotypes and coronary heart disease. The postprandial lipid response was modified by polymorphisms within the genes for apolipoprotein AI, apolipoprotein E, apolipoprotein B, apolipoprotein CI, apolipoprotein CIII, apolipoprotein AIV, apolipoprotein AV, lipoprotein lipase, hepatic lipase, fatty acid-binding protein-2, the fatty acid transport proteins, microsomal triglyceride transfer protein and scavenger receptor class B type I. We also discuss recent advances in the effects of gene regulation using knockdown animal models on postprandial lipoprotein metabolism. SUMMARY: The review discusses several of these factors as well as the potential impact of gene polymorphism on the variability of postprandial lipoprotein metabolism as intermediate phenotypes for coronary heart disease. The variability in postprandial lipid response is highly complex. Future studies will need to be large if they are to assess the effects of multiple polymorphisms.     

Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha

The high-cholesterol/high-fat Western diet has abetted an epidemic of atherosclerotic cardiovascular disease, the leading cause of death in industrialized nations. Liver X receptors (LXRs) are oxysterol sensors that are required for normal cholesterol and triglyceride homeostasis, yet synthetic LXR agonists produce undesirable hypertriglyceridemia. Here we report a previously unrecognized role for hepatic LXRalpha in the links between diet, serum lipids, and atherosclerosis. A modest increase in hepatic LXRalpha worsened serum lipid profiles in LDL-receptor null mice fed normal chow but had the opposite effect on lipids and afforded strong protection against atherosclerosis on a Western diet. The beneficial effect of hepatic LXRalpha was abrogated by a synthetic LXR agonist, which activated SREBP-1c and its target genes. Thus, the interplay between diet and hepatic LXRalpha is a critical determinant of serum lipid profiles and cardiovascular risk, and selective modulation of LXR target genes in liver can ameliorate hyperlipidemia and cardiovascular disease.