Reduced Cholesterol Concentrations Research Articles

The Influence of β-Cyclodextrin on the Reduction of Cholesterol Content in Egg and Duck Liver Pâté.

The use of β-cyclodextrin (β-CD) to reduce cholesterol is increasing in food research due to its affinity for non-polar molecules such as cholesterol. The objective of this study was to study the ability of β-CD to remove cholesterol in natural egg, powdered egg, and duck liver pâté and its effect on individual fatty acids. A concentration of 5% of β-CD was found to be a suitable amount to remove 80.04 ± 4.96–82.12 ± 5.36% of cholesterol from yolk and powdered eggs and 80.21 ± 5.28% of cholesterol from duck liver pâté. β-CD complexed to cholesterol was precipitated and removed by centrifugation. Individual fatty acid compositions did not differ (p < 0.05) between the controls and the products treated with 5% β-CD.

Ultrasound-mediated interfacial protein adsorption and fat crystallization in cholesterol-reduced lard emulsion.

Lard with a substantially reduced cholesterol content through aqueous enzyme extraction is an attractive source of lipid in healthy and nutritious emulsion food product development. The objective of this study was to elucidate the crystallization behavior (4-20 °C) of emulsions prepared from low-cholesterol lard in relation to protein emulsifier (2 and 4% whey protein isolate, WPI) and ultrasound (475 w, 5 min) treatments. The physicochemical properties and fat crystallization pattern of the emulsions were investigated. Emulsions with 4% WPI were superior to those with 2% WPI on interfacial adsorption and crystal size reduction. Ultrasonic treatment of prepared emulsions further decreased fat crystal size, promoted small and uniform crystal distribution, and slightly destabilized emulsions. Protein concentration and ultrasonic treatment had no obvious effect on crystal transition from β' to the more stable β-form based on X-ray diffraction. The melting properties determined by differential scanning calorimetry indicated that emulsified lard had a lower onset melting temperature than bulk lard, and with ultrasound treatment, the melting enthalpy increased remarkably. The ultrasound-induced change in fat crystalline structure and emulsion meta-stability may be valuable to the manufacture of healthy, emulsion-incorporated food products.

The Effect of Guava on the Improvement of Lipid Profile in Hypercholesterolemic Rats

Red guava is a fruit species with high vitamin C content and the highest fibers, in particular, soluble fiber (pectin) among tropical fruits and cereals. The soluble fiber is hypocholesterolemic in the body. Therefore, it has the potential to reduce cholesterol content. This study aimed to assess the potential of red guava in reducing cholesterol content in hypocholesterolemic rats. This study applied a pure experiment using a randomized pretestposttest group design on hypocholesterolemic Sprague Dawley rats. The rats were fed with 0.72 g of red guava and pectin supplement as a comparison. The total cholesterol content, LDL, HDL and triglyceride were measured by CHOD-PAP and GPO-PAP methods. Data analysis used t-test and ANOVA with significance rate of 0.05. Red guava intake to the hypocholesterolemic rats significantly reduced the contents of: total cholesterol to 57.8 mg/dL (32%), LDL to 25.5 mg/dL (43%), triglyceride to 19.7 mg/dL (18%). Conversely, it significantly increased HDL content to 10.6 mg/dL (18%). The red guava has proven to give hypocholesterolemic effect by reducing the total cholesterol LDL and triglyceride; Conversely, it significantly increased HDL.

Administration of Various Feed Additives on Cholesterol Content of Meat and Fat Abdomen of Local Chicken (Gallus domesticus)

Cholesterol consumed more than required body will influence health problem such as arteriosklerosis and finally resulted in coronary hearth. The purpose of this study is to evaluate the concentration of cholesterol and fat abdomen local chicken administrated various levels of feed additives. Totally 200 chickens from growth study were selected for 20 chickens at the age of 90 d for further cholesterol and fat abdomen analysis. This study was designed by using completely randomized consisting of 4 treatments and 5 replications. Four treatments in this study was administration of feed additives either in the water or in the feed (A0 = control-vita chick 0.7 gram/liter; A1= 20 ml/liter probio-FM; A2= 0.08% MOS (manan-oligosakarida)/kg in feed and A3= herbal leuser KI 5 ml/liter). Variables observed in this study were the content of cholesterol and fat abdomen. All data were statistically analyzed using SPSS and differences between treatments were stated (P&lt;0.05) by using Duncan Multiple Range Test (DMRT). The results of the study indicated that administration of various feed additives significantly effected (P&lt;0.05) on the cholesterol content of breast meat of local chickens. The average of breast meat cholesterol content was 52 mg/100g, 44 mg/100g, 43 mg/100g and 46 mg/100g for A0, A1, A2 and A3 respectively. Administration of administration of various feed additives significantly reduced (P&lt;0.05) the percentage of fat abdomen of local chickens with the percentage of 0.78%, 0.36%, 0.27% and 0.42% for A0, A1, A2 and A3 respectively. This study concluded that administration various feed additives significantly reduced cholesterol content and the percentage of fat abdomen with the lowest of cholesterol content 43 mg/100g and the lowest percentage of fat abdomen 0.27% for prebiotic treatment.

Tofu and fish oil independently modulate serum lipid profiles in rats: Analyses of 10 class lipoprotein profiles and the global hepatic transcriptome

Soy protein and fish oil are food components that decrease the risk of cardiovascular disease. Previous studies demonstrated that these food components reduced serum cholesterol levels and suppressed hepatic lipogenesis. However, the underlying mechanisms of action of these food components remain unclear. Ten classes of serum lipoprotein profiles showed that dietary tofu, a soybean curd, suppressed cholesterol absorption, while fish oil reduced most of the lipoprotein classes in rats. Tofu and fish oil both halved the level of the lipoprotein class LAC1 (LDL-anti-protease complex), a 15-nm LDL-anti-protease complex, which is speculated to be a cause of atherosclerosis. Moreover, a global transcriptome analysis revealed that tofu inhibited the mRNA expression of genes involved in hepatic lipogenesis, while fish oil stimulated that of genes related to fatty acid degradation. Therefore, tofu and fish oil independently regulate lipid metabolism. The decrease observed in LAC1 may have been due to reduced cholesterol absorption in the tofu diet group and the interference of lipogenesis via the activation of polyunsaturated fatty acid detoxification in the fish oil group.

Cholesterol-lowering potentials of Lactobacillus strain overexpression of bile salt hydrolase on high cholesterol diet-induced hypercholesterolemic mice.

Hypercholesterolemia is closely associated with cardiovascular disease. Supplementation with probiotics has been shown to contribute to improving lipid metabolism. The probiotic mechanisms of cholesterol reduction are complicated and remain unclear. One of the potential probiotic mechanisms for cholesterol reduction is the deconjugation of bile salts. We previously found a high bile salt hydrolase (BSH) activity of Lactobacillus casei pWQH01 (overexpression of bsh1) and Lactobacillus plantarum AR113, but found no BSH activity for Lactobacillus casei LC2W in vitro. Therefore, we decided to investigate whether the high BSH activity of L. plantarum AR113 and L. casei pWQH01 could exert a cholesterol-reducing effect in vivo. Compared to the high-cholesterol diet (HCD) group, AR113 and pWQH01 groups had a significantly lower body weight (BW), serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and atherogenic index (AI), whereas the LC2W group had a poor capability to mitigate the blood lipid levels in the hypercholesterolemic mice. In addition, the AR113 and pWQH01 groups decreased the hepatic levels of TC and LDL-C and improved hepatic steatosis compared with the HCD group. To explore their cholesterol-lowering mechanisms of action, we determined the expression levels of these genes on the cholesterol metabolic pathways. AR113 and pWQH01 groups downregulated the expression of farnesoid X receptor (FXR) and small heterodimer partner (SHP) genes, but upregulated the expression of the cholesterol 7α-hydroxylase (CYP7A1) gene in the liver. Simultaneously, the expression of cholesterol liver X receptor (LXR) and low density lipoprotein receptor (LDLR) genes was upregulated in the liver. These results indicated that L. plantarum AR113 and L. casei pWQH01 could inhibit the cholesterol absorption and accelerate the cholesterol transportation. Taken together, these findings suggest that Lactobacillus strain overexpression of bile salt hydrolase has beneficial effects against hypercholesterolemia by reducing cholesterol absorption and increasing cholesterol catabolism.

Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis

Studies suggest that altered renal lipid metabolism plays a role in the pathogenesis of diabetic kidney disease and that genetic or pharmacological induction of cholesterol efflux protects from the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether altered lipid metabolism contributes to renal failure in the Col4a3 knockout mouse model for Alport Syndrome. There was an eight-fold increase in the cholesterol content in renal cortexes of mice with Alport Syndrome. This was associated with increased glomerular lipid droplets and cholesterol crystals. Treatment of mice with Alport Syndrome with hydroxypropyl-β-cyclodextrin (HPβCD) reduced cholesterol content in the kidneys of mice with Alport Syndrome and protected from the development of albuminuria, renal failure, inflammation and tubulointerstitial fibrosis. Cholesterol efflux and trafficking-related genes were primarily affected in mice with Alport Syndrome and were differentially regulated in the kidney cortex and isolated glomeruli. HPβCD also protected from proteinuria and mesangial expansion in a second model of non-metabolic kidney disease, adriamycin-induced nephropathy. Consistent with our experimental findings, microarray analysis confirmed dysregulation of several lipid-related genes in glomeruli isolated from kidney biopsies of patients with primary FSGS enrolled in the NEPTUNE study. Thus, lipid dysmetabolism occurs in non-metabolic glomerular disorders such as Alport Syndrome and FSGS, and HPβCD improves renal function in experimental Alport Syndrome and FSGS.

Physicochemical traits and sensory quality of commercial butter produced in the Azores

In the volcanic islands of the Azores archipelago, pasture is available the entire year and affects the composition of bovine milk fat. The composition of cows' milk butter manufactured in this region was evaluated. All brands showed excellent microbiological and oxidative quality. The fatty acid profile range presented a low n-6/n-3 ratio (1.81–3.38), low atherogenic (2.86–3.11) and thrombogenicity (3.27–3.60) indices and reduced cholesterol content (136–143 mg 100 g−1). In addition, Azorean butters have a high content of conjugated linoleic acid (0.44–0.64 mg 100 g−1), β-carotene (0.12–0.17 mg 100 g−1) and α-tocopherol (1.40–2.20 mg 100 g−1). Sensory analysis revealed high scores for appearance, consistency and flavour of all brands. These results indicate that Azorean butters produced from cows’ milk based on grass-feeding have a potentially healthier fat content and a desirable flavour that, associated with its “natural image”, may be promoted for product differentiation.

CYP46A1 protects against NMDA-mediated excitotoxicity in Huntington's disease: Analysis of lipid raft content

Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease caused by abnormal polyglutamine expansion in huntingtin (mHtt) protein leading to degeneration of striatal neurons. Excitotoxicity, consecutive to overstimulation of N-methyl d-aspartate receptors (NMDARs) has a pivotal role in many neurological disorders including HD. Mutant Htt causes enhanced NMDA sensitivity, alteration of NMDAR expression and localization in neurons. Excitotoxic events initiate neuronal death in numerous ways, including activation of apoptotic cascades. Among the NMDAR subunits involved in glutamatergic-mediated excitotoxicity, GluN2B has been extensively reported. In addition to excitotoxicity, alteration of cholesterol metabolism has been observed in HD, with a decrease of cholesterol precursor synthesis along with an increase of cholesterol accumulation, which is deleterious for neurons. Expression of Cholesterol Hydroxylase enzyme, CYP46A1, which converts cholesterol into 24 S-hydroxycholesterol is down-regulated in HD. We found that CYP46A1 overexpression is beneficial in HD neurons and mouse model, but the mechanisms involved still remain unclear. In this study we addressed the effect of CYP46A1 on NMDAR-mediated excitotoxicity in HD primary neurons and its role in modulating cholesterol and localization of GLUN2B in lipid rafts. We showed that CYP46A1 is protective against NMDAR-mediated excitotoxicity in two different HD neuronal cell models. Cholesterol as well as GluN2B level in lipid raft, are significantly increased by mHtt. Despite a clear effect of CYP46A1 in reducing cholesterol content in lipid raft extracts from wild type neurons, CYP46A1 overexpression in HD neurons could not normalize the increased cholesterol levels in lipid rafts. This study highlights the beneficial role of CYP46A1 against NMDAR-mediated excitotoxicity and gives further insights into the cellular mechanisms underlying CYP46A1-mediated neuroprotection.

Beneficial Impact and Molecular Mechanism of Bacillus coagulans on Piglets' Intestine.

The aim of this research was to investigate the beneficial impact and molecular mechanism of B. coagulans on piglets’ intestine. Twenty-four 21 days old weaned piglets were allotted to three treatments: Control group (basal diet), B6 group (basal diet + 2 × 106 CFU/g B. coagulans), and the B7 group (basal diet + 2 × 107 CFU/g B. coagulans). The results showed that, compared with the control group, the B7 group had a reduced cholesterol content and gamma glutamyl transpeptidase (GGT) in plasma (p < 0.05); the B6 and B7 groups had a significantly decreased diarrhea rate and diamine oxidase (DAO) activity in plasma (p < 0.05), increased villus height in ileum and decreased crypt depth in the jejunum (p < 0.05); increased activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the content of malondialdehyde (MDA) and H2O2 in the intestine (p < 0.05). These data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients’ metabolism, maintaining intestinal integrity, and alleviating oxidative stress and diarrhea. Further research of molecular mechanisms showed changing expression levels of related proteins and genes, suggesting that these could be involved in the regulation of the impact. The community composition of the gut microbiota was also found to be altered in several operational taxonomic units within the genus, Prevotella (order Bacteroidales), and the order, Clostridiales.

Stress, anger and Mediterranean diet as predictors of metabolic syndrome

Background and objectiveMetabolic syndrome (MetS) is a cluster of metabolic conditions that include abdominal obesity, reduction in cholesterol concentrations linked to high density lipoproteins (HLDc), elevated triglycerides, increased blood pressure and hyperglycaemia. Given that this is a multicausal disease, the aim of this study is to identify the psychological, emotional and lifestyle variables that can have an influence on the different MetS components. Patients and methodsA cross-sectional study with 103 patients with diagnostic criteria for MetS (47 male and 56 female). Anthropometric, clinical and analytical measurements were collected to assess the variables associated with MetS. The main psychological and emotional variables were also assessed. ResultsDifferent multiple linear regression tests were performed to identify which variables were predictive of MetS. The dependent variables were body mass index (BMI), abdominal circumference, HDLc, and quality of life, and the predictive variables were psychological stress, anger and adherence to a Mediterranean diet. The results showed that psychological stress was a predictor of quality of life (β=−0.55, p≤0). Similarly, anger was a predictor of BMI (β=0.23, p=.047) and abdominal circumference (β=0.27, p=.021). As expected, adherence to a Mediterranean diet was a predictor of HDLc (β=0.2, p=.045) and of quality of life (β=−0.18, p=.031). ConclusionsThe results confirm a link between adherence to certain dietary habits and lifestyle, however they go one step further and show the importance of psychological and emotional factors like psychological stress and anger in some MetS components.

A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption.

A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the LIMA1 (also known as EPLIN or SREBP3) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane. LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake. Similar to the human phenotype, Lima1-deficient mice displayed reduced cholesterol absorption and were resistant to diet-induced hypercholesterolemia. Through our study of both mice and humans, we identify LIMA1 as a key protein regulating intestinal cholesterol absorption.

Single Quantum Dot Tracking Reveals Serotonin Transporter Diffusion Dynamics are Correlated with Cholesterol-Sensitive Threonine 276 Phosphorylation Status in Primary Midbrain Neurons.

Serotonin transporter (SERT) terminates serotonin signaling in the brain by enabling rapid clearance of the neurotransmitter. SERT dysfunction has been associated with a variety of psychiatric disorders, including depression, anxiety, and autism. Visualizing SERT behavior at the single molecule level in endogenous systems remains a challenge. In this study, we utilize quantum dot (QD) single particle tracking (SPT) to capture SERT dynamics in primary rat midbrain neurons. Membrane microenvironment, specifically membrane cholesterol, plays a key role in SERT regulation and has been found to affect SERT conformational state. We sought to determine how reduced cholesterol content affects both lateral mobility and phosphorylation of conformationally sensitive threonine 276 (Thr276) in endogenous SERT using two different methods of cholesterol manipulation, statins and methyl-β-cyclodextrin. Both chronic and acute cholesterol depletion increased SERT lateral diffusion, radial displacement along the membrane, mobile fraction, and Thr276 phosphorylation levels. Overall, this work has provided new insights about endogenous neuronal SERT mobility and its associations with membrane cholesterol and SERT phosphorylation status.

Supplementation with curcumin inhibits intestinal cholesterol absorption and prevents atherosclerosis in high-fat diet–fed apolipoprotein E knockout mice

Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Reduced intestinal cholesterol absorption has been shown to exert strong cholesterol-lowering and antiatherogenic effects. Previously, we reported that curcumin reduced cholesterol absorption in high-fat diet–fed hamster by downregulating the intestinal expression of Niemann-Pick C1-like 1. Here, we tested the hypothesis that supplementation with curcumin can also reduce intestinal cholesterol absorption in high-fat diet–fed apolipoprotein E knockout (ApoE−/−) mice and prevent atherosclerosis development. ApoE−/− mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Aortic sinus sections revealed that curcumin supplementation reduced the extent of atherosclerotic lesions by 45%. Curcumin treatment also reduced cholesterol accumulation in the aortas by 56% and lowered plasma total cholesterol and low-density lipoprotein cholesterol levels. Moreover, the antiatherogenic and cholesterol-lowering effects of curcumin coincided with a significant decrease in intestinal cholesterol absorption. It was reduced by nearly 51%, and the decreased cholesterol absorption was modulated by inhibiting the intestinal expression of Niemann-Pick C1-like 1, predominantly in the duodenal and jejunal segments of the small intestine. These findings support the hypothesis that curcumin supplementation reduces intestinal cholesterol absorption and prevents atherosclerosis in high-fat diet–fed ApoE−/− mice. Curcumin affords a potent antiatherogenic action by inhibiting intestinal cholesterol absorption in the mouse.

Abstract 232: Development and Validation of a Mathematical Model Representing Complex Cellular Interactions Within the Artery Wall: in Silico Approach to Test Targeted Interventions

Atherosclerotic cardiovascular diseases remain the number one cause of morbidity and mortality despite significant advances in lipid management. Complex cellular interactions occur within the artery wall requiring timely infiltration/egress of immune cells and lipoproteins within a changing inflammatory milieu that determine the progression of an atherosclerotic plaque. Lack of detailed understanding of the multiple processes involved and their potential interactions has hindered development of targeted therapies. The objective of this study was to develop a computational model of the sequential influx of immune cells in response to a trigger to permit a system-level analyses of the processes involved using ordinary differential equations (ODEs). Thioglycollate induced peritonitis was used as a model to examine the infiltration of immune cells and phenotypic polarization of macrophages in response to a stimulus. Peritoneal exudates obtained at 10 different time-points over 7 days were analyzed by FACS to determine the distribution of neutrophils, macrophages and Ly6C Hi (M1) or Ly6C Lo (M2) polarization. Weighted least squares of the different parameters were used to calibrate the model developed in our laboratory (Panel A) to simulate inflammation/repair during sepsis using the Levenberg-Marquardt algorithm. Panels B-D show the “match” of the experimental data to the calibrated model demonstrating the validity of this model. Since the ODEs are derived from a combination of known and hypothesized kinetics of the biological system, model the changes in physiological variables over time and are based on biological interactions, our calibrated mathematical model will permit the evaluation of changes in one or more targeted parameters in silico on immune cell distribution/phenotype. Efficacy of various macrophage-specific interventions (e.g., reduction in cholesterol content or inflammation) can be predicted prior to preclinical experimentation.

The phospholipase A2 pathway controls a synaptic cholesterol ester cycle and synapse damage.

The cellular prion protein (PrPC) acts as a scaffold protein that organises signalling complexes. In synaptosomes, the aggregation of PrPC by amyloid-β (Aβ) oligomers attracts and activates cytoplasmic phospholipase A2 (cPLA2), leading to synapse degeneration. The signalling platform is dependent on cholesterol released from cholesterol esters by cholesterol ester hydrolases (CEHs). The activation of cPLA2 requires cholesterol released from cholesterol esters by cholesterol ester hydrolases (CEHs), enzymes dependent upon platelet activating factor (PAF) released by activated cPLA2 This demonstrates a positive feedback system in which activated cPLA2 increased cholesterol concentrations, which in turn facilitated cPLA2 activation. PAF was also required for the incorporation of the tyrosine kinase Fyn and cyclooxygenase (COX)-2 into Aβ-PrPC-cPLA2 complexes. As a failure to deactivate signalling complexes can lead to pathology, the mechanisms involved in their dispersal were studied. PAF facilitated the incorporation of acyl-coenzyme A:cholesterol acyltransferase (ACAT)-1 into Aβ-PrPC-cPLA2-COX-2-Fyn complexes. The esterification of cholesterol reduced cholesterol concentrations, causing dispersal of Aβ-PrPC-cPLA2-COX-2-Fyn complexes and the cessation of signalling. This study identifies PAF as a key mediator regulating the cholesterol ester cycle, activation of cPLA2 and COX-2 within synapses, and synapse damage.

Inorganic Vanadium Supplementation in Crossbred Calves: Effects on Antioxidant Status, Immune Response and Haemato-Biochemical Attributes.

The aim of the study was to assess the effect of inorganic vanadium (V) supplementation on antioxidant enzymes, immune status, and haemato-biochemical attributes of growing crossbred calves. Twenty-four male Karan Fries calves (Tharparkar × Holstein Friesian) (initial body mass 72.83 ± 2.5kg; age 3-9month) were randomly allocated to four groups: the control (received basal diet devoid of supplemental V), the 3ppm (received basal diet with 3mg/kg V), the 6ppm (received basal diet with 6mg/kg V) and the 9ppm group (received basal diet with 9mg/kg V). All the calves were fed for 150days as per ICAR (2013) feeding standards to meet their nutrient requirements for 500g growth rate/day. Peripheral blood samples were collected at the start of experiment and subsequently at 30, 60, 90, 120 and 150days post-V supplementation for determination of antioxidant enzyme activity, immunological parameters and haemato-biochemical attributes. Results indicated that dietary supplementation of V did not affect daily gain, feed intake and haematological parameters. Crossbred calves fed with 9mg V/kg diet showed reduced (P <0.05) plasma total cholesterol concentration; however, plasma total protein and glucose concentration remained unaltered. Glutathione peroxidase (GPx) activity as well as immunoglobulin G (IgG) concentration was significantly (P <0.05) higher in group supplemented with 9mg V/kg DM; however, superoxide dismutase (SOD), catalase activity and total plasma immunoglobulin (Ig) concentration were similar in all experimental group. Dietary V supplementation showed a negative relation with plasma thiobarbituric acid reactive substances (TBARS) concentration, whereas non-esterified fatty acid (NEFA) concentration remained unaltered among all groups. Plasma V level increased (P <0.05) with increasing dietary V levels without affecting levels of Ca, Mg, Fe, Cu and Zn. In conclusion, a dietary addition of 9mg V/kg DM reduced cholesterol content and improved antioxidant and immune response in growing crossbred calves.

Selected natural agents used for cholesterol controls

PurposeVarious studies suggest that some of natural agents create a specific action of hypocholesterolemic effect. Considering this fact, the aim of this paper is to work on describing selected natural agents that may reduce cholesterol concentrations by different mechanism of actions.Design/methodology/approachThe advantages, phytochemical components and the mechanisms of the agents were reviewed and supported from the findings of the in vitro, double-blind and clinical studies from published journals, books and articles. The journals used in this review were published between 1987 and 2016, and are available from PubMed, ScienceDirect and Google Scholar.FindingsPlant stanols and sterols, turmeric, fenugreek, avocado, tomato, artichoke, red yeast rice and garlic showed a positive effect in maintaining cholesterol levels by specific mechanisms or actions. These agents each had a specific action in creating a hypocholesterolemic effect either by inhibition of the enzyme significant to the synthesis process, disturbing the absorption of cholesterol, conversion of cholesterol to other related forms and through the reduction of the oxidative stress.Research limitations/implicationsHowever, this field still needs more studies as, currently, there is not any detailed information regarding the main active ingredients responsible for the mechanism to reduce cholesterol levels in humans.Originality/valueThis paper enlightens the authors’ understanding of some natural agents that have the potential to be used in controlling cholesterol.

Fatty acids modulate the expression levels of key proteins for cholesterol absorption in Caco-2 monolayer

BackgroundFatty acids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is mediated by several transporter proteins. Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a major contributor to this process. The current study investigates the unknown mechanism by which fatty acids modulate cholesterol absorption.MethodsWe evaluated the effects of six fatty acids palmitic acid (PAM), oleic acid (OLA), linoleic acid (LNA), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cholesterol uptake and transport in human enterocytes Caco-2 cells, and on the mRNA expression levels of NPC1L1, others proteins (ABCG5, ABCG8, ABCA1, ACAT2, MTP, Caveolin 1, Annexin-2) involved in cholesterol absorption, and SREBP-1 and SREBP-2 that are responsible for lipid metabolism.ResultsThe polyunsaturated fatty acids (PUFAs), especially for EPA and DHA, dose-dependently inhibited cholesterol uptake and transport in Caco-2 monolayer, while saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) had no inhibitory effects. EPA and DHA inhibited cholesterol absorption in Caco-2 monolayer might be caused by down-regulating NPC1L1 mRNA and protein levels, which were associated with inhibition of SREBP-1/− 2 mRNA expression levels.ConclusionResults from this study indicate that functional food containing high PUFAs may have potential therapeutic benefit to reduce cholesterol absorption. Further studies on this topic may provide approaches to control lipid metabolism and to promote health.

Sterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of Rifampicin in mice.

Sterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27-hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/ Apolipoprotein E (ApoE) double knockout (KO) mice fed with Western diet (WD), the atherosclerotic phenotype found in ApoE KO mice was reversed. As protective mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1 heterozygote/ApoE KO (het) mice, with reduced Cyp27a1 expression and normal levels of Cyp7a1 and Cyp3a11, developed more severe lesions than ApoE KO mice. To analyze the contribution of Cyp3a11 to the protection of atherosclerosis development, Cyp3a11 was induced by Rifampicin (RIF) in ApoE KO and het mice. Males were fed with WD and treated daily with RIF (10 mg/kg ip) or vehicle for 4 weeks. Atherosclerosis was quantified in the aortic valve. Plasma lipids and 27-hydroxycholesterol (27-OHC), expression of cytochromes P450 and genes involved in cholesterol transport and bile acids (BAs) signaling in liver and intestine, and intestinal cholesterol absorption were analyzed. RIF increased expression of hepatic but not intestinal Cyp3a11 4-fold in both genotypes. In ApoE KO mice treated with RIF, we found a 2-fold decrease in plasma cholesterol, and a 2-fold increase in high-density lipoprotein/low-density lipoprotein ratio and CY27A1 activity. Intestinal cholesterol absorption remained unchanged and atherosclerotic lesions decreased approximately 3-fold. In het mice, RIF had no effect on plasma lipids composition, CYP27A1 activity, and atherosclerotic plaque development, despite a reduction in cholesterol absorption. In conclusion, the antiatherogenic effect of Cyp3a11 induction by RIF was also dependent on Cyp27a1 expression.