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Introduction: Data on sodium glucose co-transporter 2 inhibitors impact on lipids in patients with diabetes are available and only a handful of studies have explored this effect in individuals with both diabetes and renal impairment; lipid parameters were not the primary focus of those earlier studies. However, there is a significant research gap specifically addressing the influence of SGLT2 inhibitors on cholesterol fractions in patients exclusively with chronic kidney disease. This aim constitutes the central objective in this particular study. Methods: In this 3-month randomized controlled study, 30 patients with stage 3 chronic kidney disease and dyslipidemia were randomly assigned to receive either dapagliflozin 10 mg or placebo. Lipid profiles, renal function, and urinary albumin levels were assessed at baseline and after 3 months. Results: Compared to baseline, patients receiving dapagliflozin for 3 months showed significant improvements in serum creatinine (p <.001) and eGFR (p =.001). Total cholesterol and LDL-C levels decreased significantly (p =.010 and.006, respectively). While albumin-creatinine ratio also decreased, this change was not statistically significant. Additionally, HDL-C and TG not significantly increased. The control group without intervention experienced deterioration in serum creatinine and eGFR (p =.008, and.011, respectively), but no statistically significant lipid changes were observed. Furthermore, post-intervention total cholesterol moderately correlated with BMI (p =.032, R =.554), yet no predictors significantly influenced lipid levels in the multiple linear regression analysis. Conclusions: Dapagliflozin has a favorable effect on cholesterol fractions in stage 3 CKD patients without diabetes mellitus and this effect was different from that observed in patients with diabetes alone. [ABSTRACT FROM AUTHOR]

Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100’s nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants. [ABSTRACT FROM AUTHOR]

The ability of the Torpedo nicotinic acetylcholine receptor (nAChR) to undergo agonist-induced conformational transitions requires the presence of cholesterol and/or anionic lipids. Here we use recently solved structures along with multiscale molecular dynamics simulations to examine lipid binding to the nAChR in bilayers that have defined effects on nAChR function. We examine how phosphatidic acid and cholesterol, lipids that support conformational transitions, individually compete for binding with phosphatidylcholine, a lipid that does not. We also examine how the two lipids work synergistically to stabilize an agonist-responsive nAChR. We identify rapidly exchanging lipid binding sites, including both phospholipid sites with a high affinity for phosphatidic acid and promiscuous cholesterol binding sites in the grooves between adjacent transmembrane α-helices. A high affinity cholesterol site is confirmed in the inner leaflet framed by a key tryptophan residue on the MX α-helix. Our data provide insight into the dynamic nature of lipid-nAChR interactions and set the stage for a detailed understanding of the mechanisms by which lipids facilitate nAChR function at the neuromuscular junction. Multiscale molecular dynamics simulations reveal rapidly exchanging lipid binding sites on the nicotinic acetylcholine receptor, including sites with high affinity for phosphatidic acid and promiscuous cholesterol sites in inter-α-helix grooves. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the joint effect of body mass index (BMI) and serum lipids levels on incident dementia. Methods: We prospectively followed up with 1,627 dementia-free community residents aged ≥60 for 5.7 years on average. At baseline, weight, and height were measured, and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected in serum. Demographic characteristics were collected through questionnaires. Dementia was based on consensus diagnosis of neurologists and neuropsychologists using DSM-IV criteria. Additive Cox proportional model was used to assess the exposure-response relationship between BMI and serum lipid levels and dementia risk. Interactions and further classifications of BMI and serum lipid levels were further presented by bivariate surface models and decision-tree models. Results: The joint effects of TC with BMI, TG with BMI, and LDL-C with BMI on the risk of incident dementia shared a similar pattern, different from their independent exposure-response curves. The joint effect of HDL-C with BMI showed an S-surface but without statistical significance. Participants with TC<5.4 mmol/L and BMI<21 kg/m2 (Hazard Ratio(HR) 1.93, 95% Confidence Interval (CI) 1.05-3.53), TC<5.4 mmol/L and BMI≥21 kg/m2 (HR 1.73, 95% CI 1.09-2.72), and TC≥5.4 mmol/L and BMI<21 kg/m2 (HR 4.02, 95% CI 2.10-7.71) were identified to have the increased risk of incident dementia compared to those with TC≥5.4 mmol/L and BMI≥21 kg/ m2. Participants with TG<1.7 mmol/L and BMI<21 kg/m2 had an increased risk of incident dementia compared to those with TG≥1.7 mmol/L and BMI≥21 kg/m2 (HR 1.98, 95%CI 1.17-3.3). Participants with LDL-C≥3.3 mmol/L and BMI<21 kg/m2 were identified to have an increased risk of incident dementia compared to those with LDL-C≥3.3 mmol/L and BMI≥21 kg/m2 (HR 3.33, 95%CI 1.64-6.78). Conclusions: Our study showed that low BMI combined with low or high levels of serum lipids may increase the risk of dementia among older adults. This finding suggests the potential impacts of these two metabolic indexes on the risk of dementia. [ABSTRACT FROM AUTHOR]

The cell membrane undergoes various changes to modify its composition and mechanical properties to control the functioning of cellular mechanisms, in which cholesterol is highly involved. We have investigated the formation of cholesterol-rich nano-domains in pure 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) solid-supported lipid bilayer (SLB) at room temperature. The mechanical properties of the lipid bilayer in the presence of 0 to 40 mol% of cholesterol have been explored by using Peak-Force Quantitative Nano-Mechanical Atomic Force Microscopy. Cholesterol-rich domains with different mechanical strengths are distinctly observed at 5% cholesterol in SLB of DOPC-cholesterol. The cholesterol-rich domains with increased height are observed up to 25% cholesterol insertion within the bilayer. Further increase of cholesterol concentration leads to shrinkage of bilayer height and moderate rise of rigidity modulus. We believe that the reduction of bilayer height is due to the decoupling of the two leaflets within the membrane at high cholesterol concentration. [ABSTRACT FROM AUTHOR]

Aim: To determine the association of fasting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) with dyslipidemia in newly diagnosed diabetes (NDD). Method: This collaborative prospective interventional clinical study was carried out by the Biochemistry Department, at the University of Karachi-Pakistan, Baqai Institute of Diabetology and Endocrinology, Karachi-Pakistan and Kansai Electric Power Medical Research Institute, Osaka, Japan. The study duration was from March 2019 to May 2020. Participants were identified on the basis of oral glucose tolerance test (OGTT) results. Of 34 participants, 17 were NDD and 17 were healthy. Demographics and anthropometric details were noted on a predesigned questionnaire. Blood samples were collected at fasting state for plasma glucose, lipid profile, HbA1c, and hormones (GIP and GLP-1). Results: The healthy participants included nine males and eight females, and the NDD participants included ten males and seven females. Mean age was 50.78±2.44 years and BMI was 28.41±0.76 kg/m2. Among healthy participants, both GIP and GLP-1 showed non-significant weak correlation for biochemical parameters. In NDD participants, GIP showed significantly negative moderate correlation with age and non-HDL and positive moderate correlation with LDL only. However, GLP-1 showed significantly positive moderate correlation with total cholesterol (r = 0.564, p = 0.018), LDL (r = 0.498, p = 0.042), HDL (r = 0.50, p = 0.041) and non-HDL (r = 0.503, p = 0.047) in NDD participants. Conclusion: The effect of GIP and GLP-1 measures on dyslipidemia were substantially different among NDD participants in our population. In the NDD group, GLP-1 is significantly moderately associated with dyslipidemia compared to GIP. [ABSTRACT FROM AUTHOR]

Background /purpose: Leptin—a protein hormone that plays vital role in the regulation of glucose homeostasis and insulin sensitivity, involved in regulating the circadian rhythms of gonadotropic, thyrotropic and adrenal axes in the endocrine system. This cross-sectional study was undertaken to correlate serum leptin levels and other demographic and biochemical parameters between prediabetic cases and control subjects of Kashmiri population. Furthermore, association of serum leptin levels with various demographic and biochemical parameters along with insulin resistance in pre-diabetic subjects was elucidated. In our study, pre-diabetic cases (n = 212) and healthy controls (n = 196) were enrolled. Methods: All study subjects underwent anthropometric assessment. Serum samples of all study subjects were analysed for biochemical parameters employing the principle of spectrophotometry and leptin levels using sandwich enzyme-linked immunosorbent assay (ELISA). Insulin levels of prediabetic cases were deduced by chemiluminescent micro particle immunoassay (CMIA) technology and thereby calculating their insulin resistance. Results: The cases had statistically increased leptin levels, lipid profile and obesity as compared to controls (p ≤ 0.05). Our study, showed a positive correlation between elevated leptin levels and increased lipid levels (total cholesterol, triglycerides; TG and very low density lipoproteins-cholesterol; VLDL-C) in prediabetics (p < 0.001). Conclusion: Beyond adiposity, leptin levels may increase the risk of pre-diabetes in Kashmiri population. Since the secretion, estimation and measurements of leptins are modest in contrast to insulin levels; therefore, leptin levels can also be included in the routine measurement as an indicator of metabolic syndrome and/or T2DM. [ABSTRACT FROM AUTHOR]

Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann–Whitney's test. 487 patients were treated with Harvoni (SOF-based, 206 patients), Epclusa (SOF-based, 124 patients), Maviret (non-SOF-based, 122 patients), or Zepatier (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni, Epclusa, and Maviret induced statistically significant elevation of TC and LDL-C, but Zepatier did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI 1.84–4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL-C (95% CI 1.39–3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12. [ABSTRACT FROM AUTHOR]

Introduction: In the Netherlands, the total number of yearly measured lipid profiles exceeds 500,000. While lipid values are strongly affected by age and sex, until recently, no up-to-date age- and sex-specific lipid reference values were available. We describe the translation of big-cohort lipid data into accessible reference values, which can be easily incorporated in daily clinical practice. Methods: Lipid values (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) from all healthy adults and children in the LifeLines cohort were used to generate age- and sex-specific percentiles. A combination of RStudio, Cascading Style Sheets and HyperText Markup Language was used to interactively display the percentiles in a responsive web layout. Results: After exclusion of subjects reporting cardiovascular disease or lipid-lowering therapy at baseline, 141,611 subjects were included. On the website, input fields were created for age, sex and all main plasma lipids. Upon input of these values, corresponding percentiles are calculated, and output is displayed in a table and an interactive graph for each lipid. The website has been made available in both Dutch and English and can be accessed at www.lipidtools.com. Conclusion: We constructed the first searchable, national lipid reference value tool with graphical display in the Netherlands to use in screening for dyslipidaemias and to reduce the underuse of lipid-lowering therapy in Dutch primary prevention. This study illustrates that data collected in big-cohort studies can be made easily accessible with modern digital techniques and preludes the digital health revolution yet to come. [ABSTRACT FROM AUTHOR]

The naked mole-rat (NMR; Heterocephalus glaber) exhibits cancer resistance and an exceptionally long lifespan of approximately 30 years, but the mechanism(s) underlying increased longevity in NMRs remains unclear. In the present study, we report unique mechanisms underlying cholesterol metabolism in NMR cells, which may be responsible for their anti-senescent properties. NMR fibroblasts expressed β-catenin abundantly; this high expression was linked to increased accumulation of cholesterol-enriched lipid droplets. Ablation of β-catenin or inhibition of cholesterol synthesis abolished lipid droplet formation and induced senescence-like phenotypes accompanied by increased oxidative stress. β-catenin ablation downregulated apolipoprotein F and the LXR/RXR pathway, which are involved in cholesterol transport and biogenesis. Apolipoprotein F ablation also suppressed lipid droplet accumulation and promoted cellular senescence, indicating that apolipoprotein F mediates β-catenin signaling in NMR cells. Thus, we suggest that β-catenin in NMRs functions to offset senescence by regulating cholesterol metabolism, which may contribute to increased longevity in NMRs. Woei-Yaw Chee et al. explore the molecular mechanisms of β-catenin involvement in cholesterol metabolism suppressing cellular senescence in naked mole-rat cells. The results of this study suggest that β-catenin in NMRs functions to offset senescence by regulating cholesterol metabolism, which may contribute to increased longevity in naked mole rats. [ABSTRACT FROM AUTHOR]

Whether the lipid profile in diabetic patients is associated with diabetic neuropathy (DN) development remains ambiguous, as does the predictive value of serum lipid levels in the risk of DN. Here, we performed the first meta-analysis designed to investigate the relationship between DN and the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Candidate studies were comprehensively identified by searching PubMed, Embase, Cochrane Library and Web of Science databases up to May 2020. Observational methodological meta-analysis was conducted to assess the relationships of TG, TC, HDL, and LDL levels with DN. Changes in blood lipids were used to estimate the effect size. The results were pooled using a random-effects or fixed-effects model. Potential sources of heterogeneity were explored by subgroup analysis. Various outcomes were included, and statistical analyses were performed using STATA (Version 12.0). Mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The Newcastle–Ottawa Scale (NOS) was applied to assess the methodological quality. I2 statistics were calculated to evaluate statistical heterogeneity. Funnel plots were utilized to test for publication bias. A sensitivity analysis was performed by omitting each study one by one. Thirty-nine clinical trials containing 32,668 patients were included in the meta-analysis. The results demonstrated that DN patients showed higher TG and lower HDL levels (MD = 0.34, 95% CI: 0.20–0.48 for TG; MD = -0.05, 95% CI: -0.08–-0.02, I2 = 81.3% for HDL) than controls. Subgroup analysis showed that patients with type 1 diabetes mellitus (T1DM) neuropathy had elevated TG levels in their serum (MD = 0.25, 95% CI: 0.16–0.35,I2 = 64.4% for T1DM). However, only patients with T1DM neuropathy had reduced serum HDL levels, and there was no significant difference in serum HDL levels between patients with T2DM neuropathy and controls (MD = -0.07, 95% CI: -0.10–-0.03, I2 = 12.4% for T1DM; MD = -0.02, 95% CI: -0.07–0.03, I2 = 80.2% for T2DM). TC and LDL levels were not significantly different between DN patients and controls (MD = -0.03, 95% CI: -0.14–0.09, I2 = 82.9% for TC; MD = -0.00, 95% CI: -0.08–0.08, I2 = 78.9% for LDL). In addition, compared with mild or painless DN patients, those with moderate or severe pain DN pain had significantly reduced serum TC and LDL levels (MD = -0.31, 95% CI: -0.49–-0.13, I2 = 0% for TC; MD = -0.19, 95% CI: -0.32–-0.08, I2 = 0% for LDL). TG levels and HDL levels did not vary considerably between patients with mild or painless DN and those with moderate or severe DN pain patients (MD = 0.12, 95% CI: -0.28–0.51, I2 = 83.2% for TG; MD = -0.07, 95% CI:-0.14–0.01, I2 = 58.8% for HDL). Furthermore, people with higher TG and LDL levels had higher risk of DN (OR = 1.36, 95% CI: 1.20–1.54, I2 = 86.1% for TG and OR = 1.10, 95% CI: 1.02–1.19, I2 = 17.8% for LDL). Conversely, high serum HDL levels reduced the risk of DN (OR = 0.85, 95% CI: 0.75–0.96, I2 = 72.6%), while TC levels made no significant difference with the risk of DN (OR = 1.02, 95% CI: 1.00–1.04, I2 = 84.7%). This meta-analysis indicated that serum lipid profile changes are among the biological characteristics of DN. Lipid levels should be explored as routine laboratory markers for predicting the risk of DN, as they will help clinicians choose appropriate therapies, and thus optimize the use of available resources. [ABSTRACT FROM AUTHOR]

Background: Exposure to arsenic orchestrates a myriad of noxious health effects, including cancer. Different parts of Irvingia gabonensis are used as herbal remedies in traditional medicine. In this study, the comparative effects of the ethanol leaf (ELEIG) and stem bark extracts (ESEIG) of Irvingia gabonensis on sodium arsenite (SA)-induced lipid profile disturbances in Wistar rats were investigated. Methods: Fifty five Wistar rats weighing between 100 g and 179 g were distributed into eleven groups (n=5). Group 1 (control) received feed and water ad libitum. Group 2 received SA at a dose of 4.1 mg/kg body weight (kgbw) for 14 days. Groups 3–11 were treated with the extracts with or without SA. Treatment was done by oral intubation for 14 days. Serum concentrations of total cholesterol (TC), triacylglycerol (TAG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), very low density lipoprotein cholesterol (VLDL-c), total lipids (TL) and atherogenic index of plasma (AIP) were used to determine the lipid profile effects of the extracts. Results: Exposure to SA caused significant (p ˂ 0.05) increases in all assayed parameters, relative to control. Post-treatment and simultaneous treatment with ELEIG and ESEIG mitigated the effects of SA. In addition, ELEIG alone at various doses produced results comparable with control values. However, ESEIG alone caused significant (p ˂ 0.05) increases in all assayed parameters, relative to control. Conclusion: These results show that ELEIG and ESEIG ameliorate SA-induced lipid profile disturbances in Wistar rats. However, long-term administration of ESEIG alone may be discouraged. [ABSTRACT FROM AUTHOR]

Stratum corneum (SC), the outermost layer of the skin, contains large variety of lipids, endowing them with the amphiphilic properties, needed to fulfil their key role in skin's barrier function. The individual role of lipid types in the barrier function is difficult to understand due to the immense heterogeneity and complexity of the lipid's organization within the SC. The lipid organization is being explored using both computational (molecular dynamics simulations) and experimental (neutron diffraction) techniques. Even though atomistic simulations provide unprecedented atomic level details, the major limitation is time and length scale that can be achieved with decent computational facility. Alternatively, coarse-grain (CG) models are currently being used to capture physics at bigger time and length scale without losing essential underlined structural information. In this study, a CG model of α-hydroxy phytosphingosines (CER[AP]) is developed based on philosophy of MARTINI force field. At first, the model is validated with various atomistic simulations and available experimental data. Later on, the model's compatibility with other major skin lipids, cholesterol, and free fatty acid (palmitic acid) is checked by simulating a mixture of lipid multilayer in presence and absence of water. The developed model of CER[AP] is able to predict key structural properties within the acceptable error limits. The phenomena of ceramide conformation transformation, cholesterol flip-flop, and specificity of lipid arrangement within the multilayered systems is observed during the simulation. This signifies the importance of model in capturing higher order structural transformations. [ABSTRACT FROM AUTHOR]

Objectives: With the acceleration of the process of aging population, to enjoy a higher health-related quality of life (HRQoL) is the goal of the elderly population and public health. Studies on relationship between HRQoL and lipid profile through a large sample of representative elderly population are scare. Objective: This study was conducted to firstly explore the relationships of lipid profile with HRQoL in Chinese centenarian population. Participants: A complete sample of 1002 participants aged over 100 years from Hainan province were recruited in the current study. Main measure: Questionnaire investigation, physical examination and blood specimen collection were carried out by family survey. The EuroQol-5 Dimensions(EQ-5D, and EQ-VAS were used to assess HRQoL. Results: In multivariate linear regression analyses, a significant association was found between EQ-5D and lipid profile, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and similar association was also existed between EQ-VAS and TC, LDL-C HDL-C, after adjustment. The score of EQ-5D and EQ-VAS in male centenarian was higher than that of the female centenarian. Conclusion: Lipid profile was positively associated with the HRQoL in Chinese centenarians. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine if 15 weeks of resistance training (RT) can alter the levels of blood lipids, body iron status, and oxidative stress in postmenopausal women with vasomotor symptoms. Postmenopausal women enrolled in a randomised controlled trial were allocated to either a sedentary control group (n = 29) or a RT group (n = 26). Blood samples were taken at week-0 and week-15 for all participants. Blood lipids and iron status were measured via routine clinical analyses. Immunoassays were used to measure oxidative stress markers. The RT group, with good compliance, was associated with significant reductions in ferritin, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein cholesterol. Moreover, ferritin was positively correlated with atherogenic lipids while negatively correlated with high-density lipoprotein in RT women. This occurred without alterations in serum iron, transferrin, transferrin-saturation, C-reactive protein and oxidative stress markers. No differences were found in control women. This study suggests that RT in postmenopausal women both reduces levels of ferritin and counteracts atherogenic lipid profiles independent of an apparent oxidative mechanism. RT may be a beneficial intervention in postmenopausal women via an interaction between ferritin and lipids; however, further investigation in a larger cohort is essential. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that hyperlipidemia is closely related to the progression of kidney disease and glomerulosclerosis has similar pathophysiological mechanisms with atherosclerosis. Atherosclerosis is essentially a chronic inflammatory process and various kidney diseases are characterized by a micro-inflammatory state. Hyperlipidemia levels are not parallel to the degree of glomerulosclerosis, inflammatory factors together with lipids may contribute to the pathogenesis of glomerulosclerosis. Therefore, it is key to clarify lipid-mediated renal injury through studying the mechanism by which inflammation affects cholesterol homeostasis at the cellular level. Intracellular lipid homeostasis involves both lipid uptake and excretion, therefore in this study, we aimed to explore whether interleukin-1β (IL-1β) promotes the uptake of oxidized low-density lipoprotein (Ox-LDL) to increase in intracellular lipid levels, and to clarify the effect of IL-1β on the expression of lectin-like oxidized LDL receptor 1 (LOX-1) and ATP-binding cassette transporter A1 (ABCA1), which may regulate cholesterol homeostasis in human mesangial cells (HMCs). Methods: The effect of IL-1β on uptake of Ox-LDL labeled with fluorescent Dil (Dil-Ox-LDL) by HMCs was observed using laser confocal microscopy. The effect of IL-1β on LOX-1 and ABCA1 expression in HMCs was detected by polymerase chain reaction and western blotting. Results: Laser confocal microscopy revealed that HMCs took up Dil-Ox-LDL. Treatment of HMCs with 5 ng/ml IL-1β for 24 h significantly increased uptake of Dil-Ox-LDL. IL-1β also promoted LOX-1 mRNA and protein expression in a dose-dependent manner. Moreover, ABCA1 mRNA and protein expression were reduced by IL-1β in lipid-loaded HMCs in a dose-dependent manner. Conclusions: IL-1β promotes the uptake of Ox-LDL and expression of LOX-1 in HMCs, whereas it inhibits expression of ABCA1 under lipid load. The imbalance in intracellular cholesterol resulted by IL-1β can in turn transform HMCs into foam cells and aggravate glomerulosclerosis. [ABSTRACT FROM AUTHOR]

Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Herein, structure-activity analysis of cholesterol analogues reveals that incorporation of C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length of alkyl tail, flexibility of sterol ring and polarity due to -OH group is required to maintain high transfection. Cryo-TEM displays a polyhedral shape for eLNPs compared to spherical LNPs, while x-ray scattering shows little disparity in internal structure. eLNPs exhibit higher cellular uptake and retention, potentially leading to a steady release from the endosomes over time. 3D single-particle tracking shows enhanced intracellular diffusivity of eLNPs relative to LNPs, suggesting eLNP traffic to productive pathways for escape. Our findings show the importance of cholesterol in subcellular transport of LNPs carrying mRNA and emphasize the need for greater insights into surface composition and structural properties of nanoparticles, and their subcellular interactions which enable designs to improve endosomal escape. Endosomal sequestration of lipid-based nanoparticles is a barrier to delivery of nucleic acids. Here the authors test an array of cholesterol variants and perform in-depth investigation of nanoparticle shape, internal structure and intracellular trafficking. [ABSTRACT FROM AUTHOR]

When in contact with biological fluids, nanoparticles dynamically absorb biomolecules like proteins and lipids onto their surface, forming a "corona". This biocorona is a dynamic and complex structure that determines how host cells respond to nanoparticles. Despite the common use of mouse models in pre-clinical and toxicological experiments, the impact of corona formed in mouse serum on the biophysical and biological properties of different size NP has not been thoroughly explored. Furthering the knowledge on the corona formed on NP exposed to mouse serum proteins can help in understanding what role it might have in in vivo studies at systemic, tissue, and cellular levels. To investigate biocorona formation, different sized polystyrene NP were exposed to mouse serum. Our data show a size- and time-dependent protein and lipid corona formation. Several proteins were identified and apolipoproteins were by far the most common group on the NPs surfaces. Moreover, we observed that cholesterol and triglycerides effectively bind to NP emphasizing that proteins are not the only biomolecules with high-affinity binding to nanomaterial surfaces. These results highlight that further knowledge on NP interactions with mouse serum is necessary regarding the common use of this model to predict the in vivo efficiency of NP. [ABSTRACT FROM AUTHOR]

Objective: To study the location and expression of receptors (SR-BI/CLA-1, SR-BII, and LDLr) and transporter (ABCA1) involved in uptake and efflux of cholesterol in human spermatozoa and assess whether obesity alters its location/expression and whether this could be related to infertility. Design: Observational study. Setting: None Patient(s): Ten controls and 20 obese patients. Intervention(s): Anthropometric parameters. Serum and semen samples were collected. Main outcome measure(s): Spermatozoon concentration, immunolocalization, and protein expression in semen. Results: Spermatozoon concentration and motility was decreased in morbidly obese patients. SR-BI/CLA-1, SR-BII, LDLr, and ABCA1 are located in the spermatozoon cell membrane and the localization does not change between obese patients and controls. Control spermatozoa showed high SR-BI expression, and less expression for the rest of the receptors analyzed, indicating that SR-BI/CLA-1 is relevant in human spermatozoon cholesterol uptake/efflux. On the contrary, spermatozoa of obese patients showed less SR-BI/CLA-1 expression than controls, and more intense positive staining for SR-BII, LDLr, and ABCA1. Finally, human sperm expresses the 130- and 82-kDa hormone-sensitive lipase (HSL) isoforms. The 130-kDa isoform is expressed in the control sperm, and the expression disappears in the obese patients. Conclusion(s): The presence of lipid receptors/transporters and HSL in human spermatozoa suggests their role in the process of maturation/capacitation. The changes in the expression of lipid receptors/transporters and the lack of the 130-kDa HSL isoform in obese patients prevent the hydrolysis of cholesterol esters internalized by these receptors, and favor their accumulation in the cytoplasm of the spermatozoa that could contribute to lipotoxicity and infertility. [ABSTRACT FROM AUTHOR]

Studies have shown that vitamin D deficiency increases the risk for lipid metabolism disorders, but this relationship has provided inconsistent results in elderly. Thus the aim was to assess the association between body composition and blood lipid profile levels on serum 25-hydrovitamin D [25(OH)D] concentration in Spanish elderly. A cross-sectional multicentre study was carried out in 383 participants (58.2% females) aged of 55-88 years. Fasting blood samples analyzed serum concentrations of 25(OH)D, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TC). Body composition parameters (fat mass, fat free mass) were obtained by bioimpedance, waist circumference (WC), physical activity and vitamin D intake were also evaluated. BMI, fat mass and total fat mass were lower in vitamin D sufficient subjects than vitamin D insufficient and deficient subjects, but this difference was not significant (p>0,05). Those with vitamin D adequate levels also showed lower TC/HDL ratio than those who had inadequate (insufficient or deficient) vitamin D levels (p=0.04). Significant association between 25(OH)D and BMI, waist circumference, total muscle mass, TC/HDL-c ratio, HDL and TG (for all p≤ 0.05) was found after controlling for some confounders. Subjects with inadequate HDL levels (<40mg/dL) showed 1.7 times higher odds than vitamin D deficiency than those with adequate HDL levels (>60mg/dL) (95% CI= 1.10 to 2.85 p= 0.017) and WC was negatively associated with vitamin D status odds ratio of 0.98 (0.96 to 1.00; p= 0.04). Vitamin D concentration was positively correlated with HDL-c and total muscle mass, as well as negatively correlated with WC, LDL-c/HDL-c and TC/HDL-c independently of age, gender and some confounders. [ABSTRACT FROM AUTHOR]

The present study was designed to discover the potential cardioprotective function of earthworm powder (EWP) extracted from Eudrilus eugeniae on isoproterenol (ISO)-induced myocardial infarction in male Wistar rats. The rats were divided into four groups, with six rats in each group. Certain rats were pretreated with EWP (200 mg/kg bwt) (Group III), and a myocardial infarction was then induced by subcutaneous injection of ISO (85 mg/kg bwt) (Group II). Oral pretreatment of 200 mg/kg bwt of EWP for 28 days significantly ( p > 0.05) improved the blood profile levels, including (a) the lipid profile of total cholesterol (TC), free fatty acids (FFA), and triglycerides (TG); (b) low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and protein; and (c) A/G ratio, glucose and uric acid levels. The electrophoretic pattern of elevated lactose dehydrogenase (LDH) levels was recovered by EWP treatment as evidenced by comparison with ISO-induced rats with cardiac damage. The above results indicate that EWP (200 mg/kg bwt) provides a cardioprotective effect by attenuating the blood profile, lipid profile, biochemical levels, and LDH patterns in rats that experienced an ISO-induced myocardial infarction. [ABSTRACT FROM AUTHOR]

Background/objectives: Omega-3 polyunsaturated fatty acids (n-3PUFA) are better absorbed when they are combined with high-fat meals. However, the role of different dietary fats in modulating the incorporation of n-3PUFA in blood lipids in humans has not been previously explored. Omega-6 polyunsaturated fatty acids (n-6PUFA) are known to compete with n-3PUFA in the metabolic pathways and for the incorporation into phospholipids, whereas saturated fats (SFA) may enhance n-3PUFA incorporation into tissues.Subjects/methods: In a randomized parallel-design trial, we aimed to investigate the long-term effects of n-3PUFA supplementation in subjects consuming a diet enriched with either SFA or n-6PUFA on fatty acid incorporation into plasma and erythrocytes and on blood lipid profiles (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides).Results: Dietary supplementation with n-3PUFA co-administered with SFA for 6 weeks resulted in a significant rise in total cholesterol (0.46±0.60 mmol/L; P=0.020) and LDL-C (0.48±0.48 mmol/L; P=0.011) in comparison with combination with n-6PUFA. The diet enriched with SFA also induced a greater increase in eicosapentaenoic acid (2.07±0.79 vs 1.15±0.53; P=0.004), a smaller decrease in docosapentaenoic acid (-0.12±0.23 vs -0.30±0.20; P=0.034) and a similar increase in docosahexaenoic acid (3.85±1.14 vs 3.10±1.07; P=0.128) percentage in plasma compared with the diet enriched with n-6PUFA. A similar effect was seen in erythrocytes. N-3PUFA supplementation resulted in similar changes in HDL-C and triglyceride levels.Conclusions: The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids. [ABSTRACT FROM AUTHOR]

Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5 % cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background/objectives: We aimed to investigate the associations of colors of fruit and vegetable (FV) subgroups, with 3-year changes of cardiometabolic risk factors.Subjects/methods: This longitudinal study was conducted in the framework of Tehran Lipid and Glucose Study, between 2006-2008 and 2009-2011, on 1272 adults. Total intake of FV and their subgroups have been assessed by a validated semi-quantitative food frequency questionnaire at baseline (2006-2008) and again at the second examination (2009-2011). Demographics, anthropometrics and biochemical measures were evaluated at baseline and 3 years later. The associations of anthropometric and lipid profile changes with FV subgroups were estimated.Results: The mean age of men and women at baseline was 39.8±12.7 and 37.3±12.1 years, respectively. Mean total intake of FV, red/purple, yellow, green, orange and white FV was 706±337, 185±95, 141±91, 152±77, 141±87 and 22±18 g/day, respectively. In men, 3-year changes of weight (β=-0.13, P=0.01) and waist circumference (β=-0.14, P=0.01) were related to intake of red/purple FV; the yellow group was inversely associated with 3-year changes of total cholesterol (β=-0.09, P=0.03) and High-density lipoprotein cholesterol (β=-0.11, P=0.03). Consumption of green and white FV was inversely related to abdominal fat gain, and atherogenic lipid parameters in men (P<0.05). In women, higher intake of red/purple FV was associated to lower weight and abdominal fat gain, fasting serum glucose and total cholesterol (P<0.05); yellow FV was also related to 3-year weight gain (β=-0.11, P=0.01).Conclusions: Various colors of FV subgroups had different effects on cardiometabolic risk factors; higher intake of red/purple FV may be related to lower weight and abdominal fat gain, and yellow, green and white FV may be related to lipid parameters. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that chemical constituents present in Pinus eldarica Medw (P. eldarica) nut possess antioxidant properties that may positively influence lipid profile. The present study was conducted to evaluate the efficacy of P. eldarica nut on the experimental atherosclerosis development in hypercholesterolemic rabbits. Methods: Forty male 6 months old white New Zealand rabbits (1.8-2 kg) were randomly assigned into five equal groups. One group was kept as control (normal) group, fed on standard rabbit diet and other 4 groups were fed on high cholesterol diet (HCD). Out of four HCD groups one group was kept as control (HCD) and other three groups were treated with different doses (50, 100 and 200 mg/kg/day) of P. eldarica nut for 8 weeks. Percentage of aortic wall area changes as indication of atherosclerosis development and fasting blood cholesterol, LDL, HDL and triglyceride levels were determined in all groups. Results: The results indicate that fasting blood cholesterol and aortic atherosclerotic involvements in 200 mg/kg/ day and 100 mg/kg/day P. eldarica nut extract treated groups significantly decreased as compared to the high cholesterol-diet control group. Conclusion: P. eldarica nut lowers blood cholesterol level and aortic atherosclerotic involvement in hypercholesterolemic rabbits. [ABSTRACT FROM AUTHOR]

Mass spectrometry imaging (MSI) allows for the direct and simultaneous analysis of the spatial distribution of molecular species from sample surfaces such as tissue sections. One of the goals of MSI is monitoring the distribution of compounds at the cellular resolution in order to gain insights about the biology that occurs at this spatial level. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) imaging of cervical tissue sections was performed using a spot-to-spot distance of 10 μm by utilizing the method of oversampling, where the target plate is moved by a distance that is less than the desorption radius of the laser. In addition to high spatial resolution, high mass accuracy (±1 ppm) and high mass resolving power (140,000 at m/z = 200) were achieved by coupling the IR-MALDESI imaging source to a hybrid quadrupole Orbitrap mass spectrometer. Ion maps of cholesterol in tissues were generated from voxels containing <1 cell, on average. Additionally, the challenges of imaging at the cellular level in terms of loss of sensitivity and longer analysis time are discussed. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of serum cholesterol and triglyceride in the assessment of cardiovascular disease risk factors in children and adolescents. Design: Case-control study. Setting: Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China. Subjects: Children from 6 years to 17 year old. 188 with simple obesity, and 431 with obesity and metabolic abnormalities. 274 age and gender-matched healthy children as controls. Methods: Receiver operating characteristic curves were used to analyze the detection of cardiovascular disease risk factors by cholesterol and triglyceride in children and adolescents. Results: The ranges of areas under receiver operating characteristic curves (AUC) for triglyceride and non-high-density lipoprotein cholesterol were 0.798-0.860 and 0.667-0.749, respectively to detect cardiovascular disease risk factors. The ranges of AUC for low-density lipoprotein cholesterol, total cholesterol, and high-density lipoprotein cholesterol were 0.631-0.718, 0.596-0.683, and 0.292-0.376, respectively. Conclusions: Triglyceride and non-high-density lipoprotein cholesterol are better than low-density lipoprotein cholesterol as predictors of cardiovascular disease risk factors in Chinese Han children and adolescents. [ABSTRACT FROM AUTHOR]

Dyslipidemia has been reported as a risk factor for incident hypertension in a few prospective studies, however, no study has specifically assessed different lipid measures including the lipid ratios, that is, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs)/HDL-C as predictors of hypertension among Middle Eastern women with high prevalences of dyslipidemia and hypertension. The study population consisted of 2831 non-hypertensive women, aged 20 years. We measured lipoproteins, and calculated non-HDL-C and the lipid ratios. The risk-factor-adjusted odds ratios for incident hypertension were calculated for every 1 standard deviation (s.d.) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Over a mean follow-up of 6.4 years, 397 women developed hypertension. An increase of 1 s.d. in TG, TC/HDL-C and TG/HDL-C increased the risk of incident hypertension by 16, 19 and 18%, respectively, and 1 s.d. increase in HDL-C decreased the risk of hypertension by 14% in the multivariable model (all P0.05). In models excluding women with diabetes and central or general obesity, TG, TG/HDL-C and TC/HDL-C remained as independent predictors of incident hypertension. In conclusion, dyslipidemia, using serum TG and TG/HDL-C, in particular, may be useful in identification of women at risk of hypertension, even in those without diabetes and central or general obesity. [ABSTRACT FROM AUTHOR]

Background and objective: Accumulating evidence suggests that serum lipids are associated with cognitive decline and dementias. However, majority of the existing information concerns only serum total cholesterol (TC) and data at the level of lipoprotein fractions and subclasses is limited. The aim of this study was to explore the levels and trends of main cholesterol and triglyceride measures and eight lipoprotein subclasses during normal aging and the development of mild cognitive impairment by following a group of elderly for six years. Design: Longitudinal. Setting: City of Kuopio, Finland. Participants: 45 elderly individuals of which 20 developed mild cognitive impairment (MCI) during the follow-up. Measurements: On each visit participants underwent an extensive neuropsychological and clinical assessment. Lipoprotein levels were measured via H NMR from native serum samples. Results: Serum cholesterol and many primarily cholesterol-associated lipoprotein measures clearly decreased in MCI while the trends were increasing for those elderly people who maintained normal cognition. Conclusion: These findings suggest that a decreasing trend in serum cholesterol measures in elderly individuals may suffice as an indication for more detailed inspection for potential signs of cognitive decline. [ABSTRACT FROM AUTHOR]

Background/Objectives:To provide a detailed lipid profile of a European adolescent population considering age, gender, biological maturity, body mass index (BMI), fat mass (FM) and percentage body fat (BF).Subjects/Methods:Within Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA), a cross-sectional study was conducted to determine fasting serum concentrations of lipids, lipoproteins and apolipoproteins in 1076 adolescents aged 12.5-17.49 years from ten European centres.Results:All serum lipid concentrations were significantly higher in girls than in boys. In boys, age was negatively correlated with high-density lipoprotein (HDL)-cholesterol and total cholesterol (TC), and positively associated with triacylglycerides (TAG) (P<0.01) whereas no significant associations were observed in girls. Biological maturity was negatively associated with TC, HDL-, low-density lipoprotein (LDL)- and non-HDL cholesterol in boys (all P<0.05) and negatively correlated with HDL-cholesterol in girls (P<0.05). BMI, FM and BF were significantly correlated with HDL-cholesterol, LDL-cholesterol, non-HDL cholesterol, apolipoprotein (apo) A1, apoB and TAG in both boys and girls.Conclusions:The lipid profile in adolescents is strongly determined by gender. Biological maturity, FM and percentage BF contribute to the variance in lipid concentrations and should be considered in future evaluations of lipid status. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) remains the leading cause of death in Germany despite statin use to reduce low-density lipoprotein cholesterol (LDL-C) levels; improving lipids beyond LDL-C may further reduce cardiovascular risk. A fixed-dose combination of extended-release niacin (ERN) with laropiprant (LRPT) provides comprehensive lipid management. We adapted a decision-analytic model to evaluate the economic value (incremental cost-effectiveness ratio [ICER] in terms of costs per life-years gained [LYG]) of ERN/LRPT 2 g over a lifetime in secondary prevention patients in a German setting. Two scenarios were modelled: (1) ERN/LRPT 2 g added to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 40 mg; (2) adding ERN/LRPT 2 g compared with titration to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 20 mg. In both scenarios, adding ERN/LRPT was cost-effective relative to simvastatin monotherapy at a commonly accepted threshold of €30,000 per LYG; ICERs for ERN/LRPT were €13,331 per LYG in scenario 1 and €17,684 per LYG in scenario 2. Subgroup analyses showed that ERN/LRPT was cost-effective in patients with or without diabetes, patients aged ≤65 or >65 years and patients with low baseline high-density lipoprotein cholesterol levels; ICERs ranged from €10,342 to €15,579 in scenario 1, and from €14,081 to €20,462 in scenario 2. In conclusion, comprehensive lipid management with ERN/LRPT 2 g is cost-effective in secondary prevention patients in Germany who have not achieved LDL-C goal with simvastatin monotherapy. [ABSTRACT FROM AUTHOR]

Objectives: The studies were carried out on 36 growing albino Wistar rats. Participants/Measurements: The animals were randomly divided into six equinumerous groups (six rats per group), and were fed six different diets for 42 days. The control group (I) was fed with AIN-93G semi-synthetic diet, whereas groups II-VI were fed with AIN-93G semi-synthetic diet supplemented with: 2, 4, 8, 16 and 32 g of methionine/kg diet, respectively. There were assessed enzymatically, in rats' blood serum, the contents of homocysteine, total cholesterol, HDL fraction and triacyloglicerols. In addition, the LDL+VLDL cholesterol content was calculated. Results: The methionine content of the diet was found to be highly positively correlated with the homocysteine content (r = 0.981) and negatively correlated with the triacylglycerols content (r = −0.916) of the experimental animals' blood serum. Conclusion: In the blood serum of rats fed the highest-methionine diet (32 g methionine/kg diet), the homocysteine content was significantly higher, as were the levels of total cholesterol and its HDL fraction, while the triacylglycerols content was lower as compared to the values obtained for rats fed other diet types. [ABSTRACT FROM AUTHOR]

Background: A detailed analysis of lipid profiles, using apolipoproteins, has not yet been conducted for prostate cancer (PCa). Since several etiological pathways have been proposed for PCa and lipids, we aimed to study this in a large Swedish cohort with 1,469 primary prostate cancers. Methods: A cohort ( n = 69,735) of all men aged 35 years or older, whose levels of triglycerides (TG) (mmol/L), total cholesterol (mmol/L), glucose (mmol/L), LDL (mmol/L), HDL (mmol/L), apoB (g/L), and apoA-I (g/L) were measured at baseline, was selected from the Apolipoprotein MOrtality RISk (AMORIS) database. About 2,008 men developed PCa. Multivariate Cox proportional hazard models were used to analyze associations between lipid components and PCa. Results: ApoA-I and HDL were inversely associated with PCa risk (e.g., HR for HDL: 0.93 (95% CI: 0.81-1.07), 0.88 (0.76-1.01), 0.81 (0.70-0.94), for second, third, and fourth quartiles compared with the first quartile; with p for trend: 0.004; HR for apoA-I: 1.00 (0.88-1.13), 0.93 (0.82-1.05), 0.88 (0.77-0.99),), for second, third, and fourth quartiles compared with the first quartile; with p for trend: 0.022). ApoB, LDL, and non-HDL were not associated with PCa risk. Conclusions: Our results show that low HDL and ApoA-I as well as increased lipid ratios are related to increased PCa risk. Experimental studies are required to tease out the underlying biological mechanisms linking these lipid components to PCa. [ABSTRACT FROM AUTHOR]

Objectives: Our purpose was to evaluate interaction of green tea consumption and abdominal obesity as related factors for lacunar infarction in Korean women. Designs: A hospital-based, incident case-control study. Settings: The Prevention and Managements of Stroke in Women study. Participants: Cases (n=233) of first incident lacunar infarction were enrolled and matched by age to stroke-free hospital controls (n=204). Measurements: The data were collected through face-to-face interviews by well trained research assistants to assess demographic, medical, lifestyle, marital status, religions status, green tea consumptions, family history of stroke, smoking status, alcohol consumption, meat and vegetable intake frequency, and past history of hypertension. Biochemical analysis, fasting blood specimens for lipid, glucose, and cholesterol level were acquired. Results: Compared with the non green tea consumer and obese women group, only the green tea consumption and non obese women group had a protective effect of lacunar infarction when adjusted for age, and age plus diet factors (OR, 0.23; 95% CI, 0.09, 0.59; OR, 0.21; 95% CI, 0.08, 0.56 respectively), but lost their significance after adjustment for age, diet factors, vascular risk factors and full model included atherogenic index factors (OR, 0.32; 95% CI, 0.09 to 1.01; OR, 0.49; 95% CI, 0.12, 1.89 respectively). Conclusions: The interaction of green tea consumption and non obesity have reduced risk of lacunar infarction, but not after adjustment for age, diet factors, vascular risk factors and atherogenic index. Also individually green tea consumption and abdominal obesity have failed to find an independent relationship with lacunar infarction after adjustment by all risk factors. Green tea consumption and green tea consumption with non obese group seemed to have a protective effect for lacunar infarction. In the results of our study, these results still remain controversial, and then we need further and larger study to get at the root of real causal effect of both relationships. [ABSTRACT FROM AUTHOR]

AbstractCholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport (RCT) that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells (VSMCs) and macrophages, which are the most important original cells of foam cells. This novel model consists of 1) a caveolae transport center, 2) an intracellular trafficking system of the caveolin-1 complex, 3) a transmembrane transport system of the ABC-A1 complex, 4) a transmembrane transport system of the SR-B1 complex, and 5) an extracelluar trafficking system of HDL/Apo-A1. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-A1. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic process of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background/Objectives:The objective of this study was to evaluate the impact of three specific ruminant (R) milk fats resulting from modification of the cow's diet on cardiovascular risk factors in healthy volunteers. R-milk fats were characterized by increased content in total trans fatty acids (R-TFAs) and parallel decrease in saturated fatty acids (SFAs).Subjects/Methods:A total of 111 healthy, normolipemic men and women have been recruited for a monocentric, randomized, double-blind and parallel intervention, 4-week controlled study. Volunteers consumed three experimental products (butter, dessert cream and cookies) made with one of the three specific milk fats (55 g fat per day). During the first week (run-in period), the subjects consumed on a daily basis dairy products containing 72% SFA/2.85% R-TFA (called ‘L0’). For the next 3 weeks of the study (intervention period), the first group continued to consume L0 products. The second group received dairy products containing 63.3% SFA/4.06% R-TFA (called ‘L4’), and the third group received dairy products containing 56.6% SFA/12.16% R-TFA (called ‘L9’).Results:Plasma concentrations of high-density lipoprotein (HDL)-cholesterol were not significantly altered by either diet (P=0.38). Compared to L0 diet, L4 diet contributed to reduce low-density lipoprotein (LDL)-cholesterol (−0.14±0.38 mmol/l, P=0.04), total cholesterol (−0.13±0.50 mmol/l, P=0.04), LDL-cholesterol/HDL-cholesterol (−0.14±0.36, P=0.03) and total cholesterol/HDL-cholesterol (−0.18±0.44, P=0.02).Conclusions:Different milk fat profiles can change cardiovascular plasma parameters in human healthy volunteers. A limited increase of the R-TFA/SFA ratio in dairy products is associated with an improvement in some cardiovascular risk factors. However, a further increase in R-TFA/SFA ratio has no additional benefit. [ABSTRACT FROM AUTHOR]

Because of the biochemical colocalization of the 5-HT3 receptor and antidepressants within raft-like domains and their antagonistic effects at this ligand-gated ion channel, we investigated the impact of lipid raft integrity for 5-HT3 receptor function and its modulation by antidepressants. Treatment with methyl-β-cyclodextrine (MβCD) markedly reduced membrane cholesterol levels and caused a more diffuse membrane distribution of the lipid raft marker protein flotillin-1 indicating lipid raft impairment. Both amplitude and charge of serotonin evoked cation currents were diminished following cholesterol depletion by either MβCD or simvastatin (Sim), whereas the functional antagonistic properties of the antidepressants desipramine (DMI) and fluoxetine (Fluox) at the 5-HT3 receptor were retained. Although both the 5-HT3 receptor and flotillin-1 were predominantly found in raft-like domains in western blots following sucrose density gradient centrifugation, immunocytochemistry revealed only a coincidental degree of colocalization of these two proteins. These findings and the persistence of the antagonistic effects of DMI and Fluox against 5-HT3 receptors after lipid raft impairment indicate that their modulatory effects are likely mediated through non-raft 5-HT3 receptors, which are not sufficiently detected by means of sucrose density gradient centrifugation. In conclusion, lipid raft integrity appears to be important for 5-HT3 receptor function in general, whereas it is not a prerequisite for the antagonistic properties of antidepressants such as DMI and Fluox at this ligand-gated ion channel. [ABSTRACT FROM AUTHOR]

Objectives:This paper describes the dietary intake of total fat, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) and cholesterol of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) in 27 centres across 10 countries.Methods:Between 1995 and 2000, a stratified random sample of 36 034 participants (age range 35–74 years) completed a standardized 24-h dietary recall, assessed by means of the computer software EPIC-SOFT. Lipid intake data were calculated using a standardized nutrient database.Results:On average, the contribution of fat to total energy intake was 34% of energy intake (%en) in women and 36%en in men for most EPIC centres, except for the British, Dutch and most Italian cohorts. Total fat (>40%en) and MUFA intakes (21%en, mainly from olive oil) were highest in Greece. Except for the Greek, Spanish and Italian centres, the average MUFA intake ranged between 10 and 13%en, with a high proportion derived from animal sources. SFA intake in women and men was lowest in the Greek, Spanish, Italian and UK cohorts with an average of 13%en (down to 9%en), and highest in the Swedish centres (16%en). The mean PUFA intake was in the range of 4–8%en, being highest in the UK health-conscious cohort. The average cholesterol intake across EPIC varied from 140 to 384 mg/d in women and 215–583 mg/d in men.Conclusions:The presented data show differences and similarities in lipid intake across the European EPIC cohorts and also show differences in food sources of dietary lipids. [ABSTRACT FROM AUTHOR]

Published studies investigating the role of APOE gene on lipid response (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides) to statin treatment have reported inconsistent results. A meta-analysis was conducted to estimate the lipid response to statin treatment among APOE genetic variants (e2 carriers, e3e3 homozygotes and e4 carriers). Twenty-four studies were included in the meta-analyses. The pooled mean reduction (Δμ) in TC from baseline was significant for all variants (e2 carriers: Δμ=−27.7% (−32.5 to −22.8%), e3e3: Δμ=−25.3% (−28.0 to −22.6%) and e4 carriers: Δμ=−25.1% (−29.3 to −21.0%)). Significant changes in LDL-C, HDL-C and triglyceride levels were also noted for all genotypes, although these changes did not differ significantly among genotypic groups. There was significant heterogeneity among the studies. Given these non-significant effects of APOE genotypes on lipid responses, there is little reason to consider the use of APOE genetic testing for guiding treatment with statins.The Pharmacogenomics Journal (2009) 9, 248–257; doi:10.1038/tpj.2009.25; published online 16 June 2009 [ABSTRACT FROM AUTHOR]

Aim: To observe the influence of mulberry (Morus indica L. cv Suguna) leaves on lipid abnormalities in STZ-diabetic rats.Materials and Methods: Treatment with dried mulberry leaf powder for a period of 8 weeks in hyperglycemic and hyperlipidemic STZ-diabetic rats.Results: Mulberry leaves regulated fasting blood glucose, ameliorated the abnormalities in lipid profile as indicated by significant (P<0.01) decrease in serum triglycerides, phospholipids, cholesterol and plasma free fatty acids by 50, 6, 31 and 22% respectively in STZ- diabetic rats compared to diabetic control rats which had significantly (P<0.01) raised levels of triglycerides, phospholipids, cholesterol and free fatty acids than the normal control rats. A marked increase in fecal bile acids (154%) was observed in mulberry treated diabetic rats compared to the diabetic control group indicating conversion of cholesterol to bile acids. In addition, mulberry supplementation significantly lowered LDL-C (67%) and VLDL-C (44%) levels and increased HDL-C (53%) and also decreased atherogenic index (58%) significantly when compared to the diabetic control group.Conclusion: Besides the diabetic rats, mulberry leaves affected lipid profile in normal rats also indicating hypolipidemic effect as a result of the synergistic action of bioactive compounds. [ABSTRACT FROM AUTHOR]

Background/Objectives:To investigate the relationships between body mass index (BMI), body fatness, ethnicity, age and blood lipids.Subjects/Method:In a subsample (N=643) of the 2002 New Zealand Child Nutrition Survey (N=3275, age 5–14 years) consisting Māori (89 boys, 69 girls), Pacific (154 boys, 194 girls) and European (71 boys, 66 girls) ethnic groups, fat-free mass (FFM) was determined by bioimpedance analysis. FFM index (FFMI, FFM/height2), fat mass index (FMI, fat mass/height2) and percentage body fat (%BF) were derived. Plasma total cholesterol and high-density lipoprotein (HDL) cholesterol were measured in 515 (80%) of these children.Results:For the same BMI, %BF was lower in Pacific Island (P<0.0001) and Māori (P<0.0001) girls compared with European but for boys there were no ethnic differences. Cross-sectional analysis across ages using Hattori charts clearly showed sexual dimorphism with girls having a higher FMI, FFMI and BMI than boys by the age of 13 year. Both Pacific girls and boys showed upward trends in FFMI and FMI with age that were significantly higher than those of the other ethnicities. Adjusting for age, sex and ethnicity, %BF was a better predictor (R2=0.090, P=0.0002) of total cholesterol than BMI (R2=0.061, P=0.049) or waist (R2=0.075, P=0.013) while FFMI was the best predictor of HDL cholesterol (R2=0.15, P<0.0001) and waist was the best predictor of the total cholesterol/HDL cholesterol ratio (R2=0.17, P<0.0001).Conclusions:Measurements of body fat and indices of body fatness additional to BMI in multiethnic paediatric populations allow changes in fat mass and FFM to be tracked and improve the ability to predict dyslipidaemia.European Journal of Clinical Nutrition (2009) 63, 627–633; doi:10.1038/ejcn.2008.15; published online 27 February 2008 [ABSTRACT FROM AUTHOR]

Egg yolk is an excellent source of phospholipids. Egg yolk powder (EYP) contains about 60% lipids, which consist of, on average, neutral lipids (65%), phospholipids (31%) and cholesterol (4%). The utilization of supercritical fluid techniques is a new way to selectively extract and fractionate non-polar and slightly polar components from foods and food products. In this study, we developed pilot-scale production methods for the isolation of high-purity egg yolk phospholipids. The method involves either liquid ethanol or supercritical fluid extraction (SFE) as isolation method and supercritical antisolvent process as precipitation method. EYP was fractionated to lipid- and protein-rich fractions using liquid ethanol or supercritical fluid as an extraction medium. In both cases, the target fraction was phospholipids dissolved in ethanol. From this solution, phospholipids were precipitated using supercritical carbon dioxide as antisolvent. Depending on the process conditions, 72–99% of the precipitate consisted of phosphatidyl choline and phosphatidyl ethanolamine, which appeared in ratios 6:1–7:1. The highest purity of phospholipids was obtained via precipitation of the isolate obtained using two-step SFE. [ABSTRACT FROM AUTHOR]

Cholesterol, certain lipids, membrane-bound and soluble proteins, as well as viruses that are synthesized in the endoplasmic reticulum (ER), reach the plasma membrane (PM) via non-classical pathway(s) that remain poorly understood. Typical for this transport is (i) its insensitivity to brefeldin A (BFA), which dissociates selected coat complexes from membranes, resulting in the disassembly of the Golgi apparatus; (ii) its rapid kinetics as compared to the classical secretory pathway; and (iii) its role in the trafficking of lipid raft components. Based on results showing that the intermediate compartment (IC) at the ER-Golgi boundary constitutes a stable tubular network that maintains its dynamics in the presence of BFA, we propose that two bidirectional Golgi-bypass pathways to the PM exist, a direct route from early IC elements, and another, reminescent of the yeast secretory pathway, from late IC elements via the endosomal system. These pathways have implications for the organization of the secretory processes in different cell types. (Part of a Multi-author Review) [ABSTRACT FROM AUTHOR]

The scavenger receptor class B type 1 ( SCARB1) gene is a key component in the reverse cholesterol transport pathway and thus plays an important role in lipid metabolism. Studies suggest that the SCARB1 gene may contribute to variation in plasma lipid levels at fasting; however, the results have been inconsistent, and it is unclear whether SCARB1 may also influence lipid response to dietary and pharmacologic interventions. In this study, we examined genetic variation in the SCARB1 gene in participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study for associations with basal lipid levels, changes in lipid measures after dietary fat intake, and fenofibrate treatment. We found that the exon 1 variant SCARB1_G2S was significantly associated with postfenofibrate change for triglycerides (TG) ( P = 0.004). Subjects bearing SCARB1_G2S minor allele A tend to have higher responsiveness to fenofibrate in lowering TG. In summary, our study suggested that the SCARB1 gene may serve as a useful marker that predicts variation in baseline lipid levels, postprandial lipid response, and response to fenofibrate intervention. [ABSTRACT FROM AUTHOR]

Abstract  The purpose of this work was to prepare salidroside nano-liposomes by the ethanol injection method. To obtain the higher encapsulating efficiency of salidroside nano-liposomes, several factors including salidroside-loading capacity, cholesterol, Tween 80, ion strength and lipid concentration were investigated. The higher encapsulating efficiency of salidroside, 45%, was obtained with cholesterol to lipid mass ratio of 1:4, Tween 80 and lipid to the molar ratio of 1:2, and ion strength in a range 20–50 mmol/L. With the optimization operation, the particles of nano-liposomes were below 100 nm and zeta potential was in the range of −10 and −20 mV. The release study of salidroside in vitro from nano-liposomes exhibited a prolonged release profile as studied over a period of 24 h. [ABSTRACT FROM AUTHOR]

To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone, three 52-week, open-label extension studies of ziprasidone in outpatients (N=185) with schizophrenia or schizoaffective disorder successfully completing one of three, 6-week switch studies were carried out. Pre-switch treatment consisted of risperidone (n=43), olanzapine (n=71), or conventional antipsychotic agents (n=71). The maximum length of exposure to ziprasidone was 58 weeks. Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6, 19, 32, 45, and 58. Weight was measured at baseline and during each follow-up visit; height was recorded at baseline for the purpose of body mass index (BMI) calculation. Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global Impression—Severity scale which were obtained at baseline and major follow-up points. Clinically significant sustained improvements in weight, BMI, total cholesterol, and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine. Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters. Mean reductions in weight from baseline to study endpoint were 9.8 kg (p<0.001) and 6.9 kg (p<0.005) for patients previously treated with olanzapine and risperidone, respectively. These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained, clinically significant improvements in weight and plasma lipids.Neuropsychopharmacology (2008) 33, 985–994; doi:10.1038/sj.npp.1301482; published online 18 July 2007 [ABSTRACT FROM AUTHOR]

Activation of Bax or Bak is essential for the completion of many apoptotic programmes. Under cytotoxic conditions, these proteins undergo a series of conformational rearrangements that end up with their oligomerization. We found that unlike inactive monomeric Bax, active oligomerized Bax is partially resistant to trypsin digestion, providing a convenient read out to monitor Bax activation. Using this assay, we studied how the lipid composition of membranes affects tBid-induced Bax activation in vitro with pure liposomes. We report that Bax activation is inhibited by cholesterol and by decreases in membrane fluidity. This observation was further tested in vivo using the drug U18666A, which we found increases mitochondrial cholesterol levels. When incubated with tBid, mitochondria isolated from U18666A-treated cells showed a delay in the release of Smac/Diablo and Cytochrome c, as well as in Bax oligomerization. Moreover, pre-incubation with U18666A partially protected cells from stress-induced apoptosis. As many tumours display high mitochondrial cholesterol content, inefficient Bax oligomerization might contribute to their resistance to apoptosis-inducing agents.Cell Death and Differentiation (2008) 15, 484–493; doi:10.1038/sj.cdd.4402280; published online 14 December 2007 [ABSTRACT FROM AUTHOR]

We have constructed a constitutive high-level-expression vector for the genus Bifidobacterium and used it to express cholesterol oxidase from Streptomyces coelicola. The promoter region of the 16S rRNA gene was amplified by inverse PCR and used for the construction of pBES16PR. The optimal ribosome-binding site (RBS) for Bifidobacterium was incorporated in pBES16PR. In order to test the efficacy of this expression vector, we constructed pBES16PR-CHOL with the structural gene for cholesterol oxidase under the control of the 16S rRNA promoter, and used it to transform Bifidobacterium longum. The gene was successfully expressed and high level of cholesterol oxidase activity was obtained in B. longum. This is the first report of an expression vector for the genus Bifidobacterium using a 16S rRNA gene promoter and successful expression of cholesterol oxidase. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the association between total cholesterol and major cardiovascular diseases among persons with and without diabetes in the Asia-Pacific region. We used data on individual participants in 30 cohort studies from the Asia-Pacific region to compute the hazards ratios and 95% CIs for participants with and without diabetes at baseline, using Cox proportional models. Analyses were stratified by sex and region (Asia vs Australia or New Zealand) and adjusted for age. Repeat measurements of total cholesterol were used to adjust for regression dilution bias. The analysis included 333,533 individuals (6.3% with diabetes at baseline) who experienced 6,074 fatal and non-fatal cardiovascular events over a median follow-up period of 4.0 years. Total cholesterol was positively associated with coronary heart disease (CHD) and ischaemic stroke, and negatively with haemorrhagic stroke in a continuous, log-linear fashion, similarly among participants with and without diabetes. Each 1 mmol/l increase above the ‘usual’ level for total cholesterol was associated with a 41% (95% CI 23–63%) and 42% (95% CI 35–50%) greater risk of CHD among participants with and without diabetes. The corresponding values for ischaemic stroke were 23% (95% CI 0–52%) and 31% (95% CI 20–44%), respectively. These results were broadly consistent for sex, age and region. Total cholesterol is associated with similarly increased risks of cardiovascular events in people with and without diabetes. While abnormal levels of other lipid fractions are frequently observed in people with diabetes, these data support aggressive lowering of total cholesterol and LDL-cholesterol levels for prevention of cardiovascular events. [ABSTRACT FROM AUTHOR]

Lipid droplets have been considered for a long time as inert intracytoplasmic deposits formed within cells under various conditions. Recently, new tools and new approaches have been used to visualize and study these intracellular structures. This revealed new aspects of lipid droplets biology and pointed out their organized structure and dynamic composition. In adipocytes, the specialized cell type for the storage of energy as fat, lipid droplets are particularly well-developed organelles and exhibit unique properties. Also discussed in this paper is the view that lipid droplets, through specific candidate constituents, can play a role in sensing the level of their lipid stores by adipocytes. [ABSTRACT FROM AUTHOR]