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Background: Obesity is more of a nutritional problem that becomes one of the double nutritional problems that must be overcome. A person with obesity tends to have a higher risk of developing hypertension, diabetes mellitus type 2, and the possibility of having a heart attack, which can show calcium scores in the heart. Objectives: This research aimed to analyze the relationship and look at differences in the incidence of DM type 2, cholesterol, and calcium scores in patients suffering from hypertension and obesity. Methods: This research used a cross-sectional study design with a quantitative method. The data collection was conducted at Siloam Hospital Surabaya (2018-2021). The determination of the sample adjusts to the criteria set by the researcher. Sample withdrawal used the purposive sampling method. The sample number was 59 men and 59 women. Research instruments were a questionnaire, interview, collecting data anthropometry, hypertension history, and cholesterol history. Results: Most of the subjects were elderly (38.1%). There were differences in the cholesterol history of women and man subjects (p=0.002). There was no noticeable difference in the history of DM type 2 in the subjects (p=0.092). There was no noticeable difference in calcium scores in the subjects (p=0.062). Most subjects other than having DM type 2 also had a history of cholesterol (73.3%). There was no noticeable correlation between cholesterol with DM type 2 in subjects (p=0.006). Most subjects with a history of DM type 2 was in a meaningful calcium score (26.6%). No association between DM type 2 and calcium score in subjects (p=0.102). Conclusions: There was no association between the incidence of diabetes mellitus type 2 and cholesterol and the incidence of DM type 2 with calcium scores in patients. There was a noticeable difference in the incidence of cholesterol in the subjects. No difference in the incidence of DM type 2 and calcium scores was found in subjects who were patients with a history of hypertension and obesity. [ABSTRACT FROM AUTHOR]

Aims  We tested the hypothesis that high directly measured remnant cholesterol is associated with increased risk of ischaemic heart disease (IHD) and myocardial infarction (MI) in the general population. We also explored whether directly measured vs. calculated remnant cholesterol is superior in identifying individuals at increased risk. Methods and results  Overall, 16 207 individuals from the Copenhagen General Population Study with both directly measured and calculated remnant cholesterol, both representing cholesterol content in triglyceride-rich lipoproteins, were followed up for 14 years to analyse the risk for IHD and MI. For directly measured and calculated remnant cholesterol, hazard ratios for individuals with concentrations ≥95th percentile vs. <40th percentile were 1.75 (95% confidence interval 1.42–2.15) and 1.76 (1.42–2.17) for IHD and 2.05 (1.50–2.80) and 1.93 (1.40–2.66) for MI. Compared to individuals with both directly measured and calculated remnant cholesterol <80th percentile (75% of the whole population), those with only directly measured remnant cholesterol ≥80th percentile (5%) had hazard ratios of 1.42 (1.15–1.75) for IHD and 1.83 (1.35–2.47) for MI. Corresponding hazard ratios for individuals with only calculated remnant cholesterol ≥80th percentile (5%) were 1.14 (0.91–1.44) and 1.14 (0.80–1.62), respectively, and corresponding hazard ratios for individuals with both directly measured and calculated remnant cholesterol ≥80th percentiles (15%) were 1.48 (1.30–1.68) and 1.67 (1.38–2.01), respectively. In individuals with high directly measured or high calculated remnant cholesterol, the median directly measured remnant cholesterol was 1.9 and 1.5 mmol/L, the median plasma triglycerides were 2.0 and 2.7 mmol/L, and the median plasma apolipoprotein B was 132 and 142 mg/dL, respectively. Conclusions  Directly measured vs. calculated remnant cholesterol identifies 5% overlooked individuals in the general population with cholesterol-rich, triglyceride-poor remnants and 1.8-fold increased risk of MI. [ABSTRACT FROM AUTHOR]

Aim Preclinical work indicates that low-density lipoprotein cholesterol (LDL-C) not only drives atherosclerosis by directing the innate immune response at plaque level but also augments proinflammatory monocyte production in the bone marrow (BM) compartment. In this study, we aim to unravel the impact of LDL-C on monocyte production in the BM compartment in human subjects. Methods and results A multivariable linear regression analysis in 12 304 individuals of the EPIC-Norfolk prospective population study showed that LDL-C is associated with monocyte percentage (β = 0.131 [95% CI: 0.036–0.225]; P = 0.007), at the expense of granulocytes (β = −0.876 [95% CI: −1.046 to −0.705]; P < 0.001). Next, we investigated whether altered haematopoiesis could explain this monocytic skewing by characterizing CD34+ BM haematopoietic stem and progenitor cells (HSPCs) of patients with familial hypercholesterolaemia (FH) and healthy normocholesterolaemic controls. The HSPC transcriptomic profile of untreated FH patients showed increased gene expression in pathways involved in HSPC migration and, in agreement with our epidemiological findings, myelomonocytic skewing. Twelve weeks of cholesterol-lowering treatment reverted the myelomonocytic skewing, but transcriptomic enrichment of monocyte-associated inflammatory and migratory pathways persisted in HSPCs post-treatment. Lastly, we link hypercholesterolaemia to perturbed lipid homeostasis in HSPCs, characterized by lipid droplet formation and transcriptomic changes compatible with increased intracellular cholesterol availability. Conclusions Collectively, these data highlight that LDL-C impacts haematopoiesis, promoting both the number and the proinflammatory activation of circulating monocytes. Furthermore, this study reveals a potential contributory role of HSPC transcriptomic reprogramming to residual inflammatory risk in FH patients despite cholesterol-lowering therapy. [ABSTRACT FROM AUTHOR]

Aims Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. Methods and results We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n  = 9748), the Multi-Ethnic Study of Atherosclerosis (n  = 3049), and the Coronary Artery Risk Development in Young Adults (n  = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45–1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08–1.34). Similar results were shown when examining discordance across clinical cutpoints. Conclusions In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated. [ABSTRACT FROM AUTHOR]

Background: Low-density lipoprotein cholesterol (LDL-C) is one of the most important types of cholesterol and has an impact on health. Certain lifestyle and dietary habits in different populations may leads to increased levels of LDL-C, particularly among those with poor education and economic statuses, such as hill tribe people in Thailand. This study aimed to estimate the prevalence of and determine the factors associated with high LDL-C levels among hill tribe people in northern Thailand.Methods: A cross-sectional study was performed to gather information from six main hill tribe populations: Akha, Lahu, Hmong, Yao, Karen, and Lisu. Individuals who were aged over 30 years and living in 30 selected hill tribe villages were invited to participate in the study. A validated questionnaire and 5-mL blood specimens were used to obtain data. Correlation analyses, chi-square tests, t-tests, and logistic regression were used to detect correlations and associations.Results: A total of 2552 participants were recruited into the study; 65.9% were females, and 64.1% were aged younger than 60 years old. Approximately 69.6% of participants had abnormal LDL-C levels; 33.6% had above-optimal levels, 24.3% had borderline high levels, 8.0% had high levels, and 3.7% had very high levels. A total of 17.4% of participants had low high-density lipoprotein cholesterol (HDL-C) and high LDL-C levels, while 14.9% had high triglyceride and LDL-C levels. After controlling for sex, age, religion, education, annual family income, and marital status in the multivariate model, three variables were found to be associated with high LDL-C levels: occupation, the amount of lard used in daily cooking, and glycated hemoglobin (HbA1c). Those who were working as agriculturalists had a 1.34-fold greater chance of having abnormal LDL-C than traders and others (95% CI = 1.09-1.34). Those who used moderate and high quantities of lard in their daily cooking had a 1.45-fold (95% CI = 1.15-1.82) and 1.31-fold (95% CI = 1.04-1.68) greater likelihood of having abnormal LDL-C levels than those who used low quantities, respectively. Those who had abnormal HbA1c levels were less likely to develop abnormal LDL-C levels than those who had normal HbA1c levels (AOR = 0.69, 95% CI = 0.51-92).Conclusions: Effective public health programs that do not conflict with the cultures of hill tribes are urgently needed, particularly programs encouraging the use of small quantities of lard for daily cooking practices. [ABSTRACT FROM AUTHOR]

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In patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as < 40 mg/dL for men and < 50 mg/dL for women. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. A total of 3731 patients (mean age 65.6 years, 75.6% men) were included. Patients with on-treatment low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) were younger and with more diabetes and higher body weight. The mean follow-up time was 2.7 years. We used restricted cubic spline curves to examine the potential non-linear association between HDL-C and adverse outcomes. Decreased HDL-C levels were associated with a significantly increased risk of CV events in women (< 49 mg/dL in women) but not in men (< 42 mg/dL in men). However, the protective effect of elevated HDL-C levels was more prominent in men than in women. In ASCVD patients with statin therapy, low on-treatment HDL-C was common in Taiwan and associated with an increased risk of CV events in women. Higher HDL-C levels provided more protective effect in men than in women. [ABSTRACT FROM AUTHOR]

The authors offer insights on a study published within the issue which investigated how low-density lipoprotein-cholesterol (LDL-C) influence proinflammatory monocyte production in the human bone marrow (BM). Topics discussed include the way LDL-C promote myelomonocytic skewing in haematopoietic stem and progenitor cells, the link between monocytosis and cardiovascular diseases (CVD), and the risk of CVD events associated with BM and splenic metabolic activity.

The authors offer insights on a study published within the issue which investigated the role of remnant cholesterol (RC) in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Topics discussed include the way RC originated from lipolytic products of triglyceride-rich lipoproteins (TRL), the multivariate models of RC, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) analyzed in the study, and the contribution of LDL to atherogenesis.

Bile is a biological fluid synthesized in the liver, mainly constituted by bile acids and cholesterol, which functions as a biological detergent that emulsifies and solubilizes lipids, thereby playing an essential role in fat digestion. Besides, bile acids are important signaling molecules that regulate key functions at intestinal and systemic levels in the human body, affecting glucose and lipid metabolism, and immune homeostasis. Apart from this, due to their amphipathic nature, bile acids are toxic for bacterial cells and, thus, exert a strong selective pressure on the microbial populations inhabiting the human gut, decisively shaping the microbial profiles of our gut microbiota, which has been recognized as a metabolic organ playing a pivotal role in host health. Remarkably, bacteria in our gut also display a range of enzymatic activities capable of acting on bile acids and, to a lesser extent, cholesterol. These activities can have a direct impact on host physiology as they influence the composition of the intestinal and circulating bile acid pool in the host, affecting bile homeostasis. Given that bile acids are important signaling molecules in the human body, changes in the microbiota-residing bile biotransformation ability can significantly impact host physiology and health status. Elucidating ways to fine-tune microbiota-bile acids-host interplay are promising strategies to act on bile and cholesterol-related disorders. This manuscript summarizes the current knowledge on bile and cholesterol metabolism by intestinal bacteria, as well as its influence on host physiology, identifying knowledge gaps and opportunities to guide further advances in the field. [ABSTRACT FROM AUTHOR]

The article describes the case of a 40-year-old man diagnosed to have pseudochylothorax or cholesterol pleural effusion. Topics include the patient's medical history and symptoms upon admission, the clinical features of cholesterol crystals found in his pleural fluid, and the treatments administered to the man. Also discussed are the differences between chylous and pseudochylous effusions.

Abstract Cholesterol is an essential component of cell membranes, and is required for mammalian pentameric ligand-gated ion channel (pLGIC) function. Computational studies suggest direct interactions between cholesterol and pLGICs but experimental evidence identifying specific binding sites is limited. In this study, we mapped cholesterol binding to Gloeobacter ligand-gated ion channel (GLIC), a model pLGIC chosen for its high level of expression, existing crystal structure, and previous use as a prototypic pLGIC. Using two cholesterol analogue photolabeling reagents with the photoreactive moiety on opposite ends of the sterol, we identified two cholesterol binding sites: an intersubunit site between TM3 and TM1 of adjacent subunits and an intrasubunit site between TM1 and TM4. In both the inter- and intrasubunit sites, cholesterol is oriented such that the 3‑OH group points toward the center of the transmembrane domains rather than toward either the cytosolic or extracellular surfaces. We then compared this binding to that of the cholesterol metabolite, allopregnanolone, a neurosteroid that allosterically modulates pLGICs. The same binding pockets were identified for allopregnanolone and cholesterol, but the binding orientation of the two ligands was markedly different, with the 3‑OH group of allopregnanolone pointing to the intra- and extracellular termini of the transmembrane domains rather than to their centers. We also found that cholesterol increases, whereas allopregnanolone decreases the thermal stability of GLIC. These data indicate that cholesterol and neurosteroids bind to common hydrophobic pockets in the model pLGIC, GLIC, but that their effects depend on the orientation and specific molecular interactions unique to each sterol. Highlights • Cholesterol binds to two sites in a model pentameric ligand gated ion channel: an intersubunit site and an intrasubunit site • Both cholesterol binding sites are shared sterol pockets • Cholesterol labels both sites in the opposite orientation as neurosteroids • Cholesterol and neurosteroids have opposite effects on thermal stability of Gloeobacter ligand gated ion channel [ABSTRACT FROM AUTHOR]

Bitter taste receptors (T2Rs) are a group of 25 chemosensory receptors expressed at significant levels in the human airways. In human airways, bitter taste receptor 14 (T2R14)-mediated physiological response in ameliorating obstructive airway disorders is an active area of investigation. Therefore, understanding various factors regulating the structure and function of T2R14 will be beneficial. We hypothesize that membrane lipids like cholesterol play a regulatory role in T2R14 signaling in airway cells. We confirmed the expression and signaling of T2R14 in primary human airway smooth muscle (HASM) cells and the human airway epithelial cell line (NuLi-1) using immunoblot analysis and intracellular calcium concentration mobilization experiments, respectively. Next, T2R14 signaling was examined in membrane cholesterol-altered environments by methyl- β-cyclodextrin or cholesterol oxidase treatments. In the cells analyzed, cholesterol depletion affected the agonist-induced T2R14 signaling, and cholesterol replenishment rescued its efficacy. An alternative approach for cholesterol depletion (with cholesterol oxidase pretreatment) also negatively affected the agonist potency at T2R14 in HASM cells. To understand the molecular mechanism of interaction between cholesterol and T2R14, we used site-directed mutagenesis coupled with functional assays and examined the role of putative cholesterol-binding motifs (CRAC and CARC) in T2R14. Functional characterization of wild-type and mutant T2R14 receptors suggests that amino acid residues K110, F236, and L239 are crucial in T2R14- cholesterol functional interaction. In conclusion, our results show that cholesterol influences the T2R14 signaling efficacy by forming direct interactions with the receptor and consequently plays a regulatory role in T2R14-mediated signaling in human airway cells. [ABSTRACT FROM AUTHOR]

Background. Previous evidence suggests that metabolic disorders in postmenopausal women could be related with low serum vitamin D levels. For example, vitamin D deficiency has been associated with increased risk factors for cardiovascular disease (CVD), mainly those related with metabolic syndrome. Objective. To assess the relationship between the serum vitamin D (25-OH-D) levels and the metabolic syndrome markers in postmenopausal women. Methods. This descriptive and cross-sectional study was conducted in 183 postmenopausal women of four municipalities from Colombian Caribbean. The serum 25-OH-D levels and the anthropometric and biochemical markers were assessed and correlated with metabolic syndrome. Results. The average value of serum vitamin D (25-OH-D) was 26.34 ± 9.08 ng/mL, and 69.95% of the women had vitamin D levels <30 ng/mL, of which 43.72% were with insufficiency (<30 to >20 ng/mL) and 26.23% with deficiency (<20 ng/mL). Of the evaluated women, the 81.42% seemed to have metabolic syndrome. Through the linear regression, one significant positive association was observed between the HDL cholesterol and the 25-OH-D levels (P=0.014). Conclusion. In the evaluated population in this study, vitamin D deficiency is related with low HDL cholesterol levels. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the underlying cause of most deaths worldwide, and they are expected to rise in the following years. Cardiovascular diseases include diseases that affect the heart, cerebral, and peripheral vessels, resulting in ischemia. On the basis of cardiovascular disease pathophysiology, there are lipoprotein metabolism abnormalities, oxidative stress, chronic inflammation, endothelium damage, and atherothrombosis. Modifiable risk factors for cardiovascular health and diseases are blood pressure, blood lipid profile, oxidative stress, inflammation, and other factors (smoking, obesity, diabetes mellitus). Atherosclerotic plaque development, vascular calcification, and vascular stiffness are caused by a long-term endothelial dysfunction and inflammatory response, which can be prevented and controlled by the diet. Fat and cholesterol are the commonly considered dietary factors in the association of the nutrition and the cardiovascular disease, although other macronutrients, especially carbohydrates and proteins, also have major effects. Nowadays, other macronutrients and micronutrients (minerals and vitamins) have roles in regulating the indicated processes (blood pressure, calcification, oxidative stress, inflammation, etc.) in cardiovascular disease prognosis. Other dietary compounds (sterols, stanols, polyphenols, carotenoids, etc.) that exist in small amounts in foods might have a role in regulating these mechanisms as well. There are also new insights about walnuts, garlic, ginger, and hawthorn as parts of a healthy diet against cardiovascular diseases. So far, there have not appeared any reviews that combine the impact of a wide variety of dietary components on cardiovascular diseases. Thus, the novel nutritional targets and interventions that focus on nutrients and other dietary compounds on potential mechanisms underlying cardiovascular diseases are discussed in this review. [ABSTRACT FROM AUTHOR]

Statins are cholesterol-lowering drugs, commonly prescribed for the significant decline of high risks leading to arrhythmia and other cardiac issues. A study conducted reveals that 40% of population among the patients of cardiovascular, got arterial fibrillation with statins and 80% without statins that are mostly prescribed along with antihypertensive and if patient is diabetic, a regime of medicine is given for the management of all probable disorders and that sometimes may lead to undesired effects specifically regarding gastric. The present study is conducted to focus the root cause of digestive disorders as either medicine or condition. In present study the method adopted was cohort study and for the purpose prescription and history of case and control groups that were both hypercholestrimic and hypertensive but diabetic and non diabetic respectively. The study out comes reveal that 67% of case group reported the after effects of digestive disorders, however interestingly no such effects were observed from control group. Data analysis showed 0.24 risk ratio. The study outcomes helped to establish the idea that statins are not accountable for digestive disorders and the outcome nullify the delusion about that specific undesired effect of statins as that were only observed in diabetic patients since diabetes itself a metabolic and comorbid disorder blamed for aggravating the digestion. [ABSTRACT FROM AUTHOR]

Fibrates are used in patients with dyslipidemia and high cardiovascular risk. However, information regarding drug response to fibrate has been highly limited. We investigated treatment results and factors associated with triglyceride reduction after fenofibrate therapy using large-scale real-world data. Patients with one or more cardiovascular risk factors, at low-density lipoprotein-cholesterol goal but with triglyceride level ≥150 mg/dL, and undergoing treatment with fenofibrate 135–160 mg for the first time were included in this retrospective observational study. The outcome variable was the percentage changes of TG levels. The achievement rate of triglyceride <150 mg/dL was additionally analyzed. Factors associated with treatment results were also analyzed. Among 2546 patients who were initially screened, 1113 patients were enrolled (median age: 61 years; male: 71%). After median follow-up of 4 months, the median change in triglyceride was -60%, and 49% of the patients reached triglyceride <150 mg/dL. After adjusting for confounding variables, female sex, non-diabetic status, coronary artery disease, lower baseline triglyceride, and no statin use were identified to be independently associated with achievement of triglyceride <150 mg/dL. Among them, female sex, non-diabetic status, and coronary artery disease were also related to median or greater percentage reduction of triglyceride. In conclusion, only half of the study patients reached triglyceride levels <150 mg/dL after real-world fenofibrate therapy. This study indicates that more attention is needed on some subgroups to obtain optimal triglyceride levels when treating with fenofibrate. [ABSTRACT FROM AUTHOR]

The transverse asymmetry (sidedness) of phospholipids in plasma membrane bilayers is well characterized, distinctive, actively maintained and functionally important. In contrast, numerous studies using a variety of techniques have concluded that plasma membrane bilayer cholesterol is either mostly in the outer leaflet or the inner leaflet or is fairly evenly distributed. Sterols might simply partition according to their differing affinities for the asymmetrically disposed phospholipids, but some studies have proposed that it is actively transported to the outer leaflet. Other work suggests that the sterol is enriched in the inner leaflet, driven by either positive interactions with the phosphatidylethanolamine on that side or by its exclusion from the outer leaflet by the long chain sphingomyelin molecules therein. This uncertainty raises three questions: is plasma membrane cholesterol sidedness fixed in a given cell or cell type; is it generally the same among mammalian species; and does it serve specific physiological functions? This review grapples with these issues. [ABSTRACT FROM AUTHOR]

A new instrument based on VUV laser desorption/ionization (VUVDI) method was used to measure the mass spectrum of the cholesterol standard and the mass spectrometry images (MSI) of intact cholesterol in a mouse esophagus tissue section and mouse zygotes. The VUVDI mass spectrum of the cholesterol standard shows dominant peaks from the parent molecules. In the case of the mouse esophagus tissue section, the ion images with a lateral resolution of ∼ 4 μm reveal that the cholesterol populates mainly in the mucosae. The experimental results indicate that the VUVDI method may provide a new MSI tool to measure the intact cholesterol in tissues and cells. [ABSTRACT FROM AUTHOR]

A phenocopy is an environmentally-defined phenotype that mimics another, genetically-determined phenotype. The severity of hypercholesterolaemia, extent of down regulation of LDL receptor expression and aortic root localisation of atherosclerosis in cholesterol-fed rabbits strikingly resemble the cardinal features of homozygous familial hypercholesterolaemia (FH) in humans, suggesting that the former is a phenocopy of the latter. This review compares the metabolic and pathological consequences of induced hypercholesterolaemia in rabbits with those of homozygous FH and contrasts their ease of reversibility on resumption of a normal diet with the refractoriness to lipid-lowering therapy of homozygotes, in whom major adverse cardiovascular events and survival depend upon the prevailing level of serum cholesterol. The monofactorial nature of the atherosclerosis in both situations corroborates Anitschkow's concept that “Cholesterin ist alles.” In contrast, atherosclerosis in heterozygous FH differs in several respects from that of homozygotes, notably the lack of aortic root involvement and in its multifactorial aetiology, with raised LDL cholesterol, male gender, low HDL cholesterol and raised lipoprotein (a) all contributing to its clinical expression. In angiographic trials of LDL-lowering therapy regression of coronary lesions was observed in FH heterozygotes whereas they progressed in non-FH subjects. Similarly, carotid artery plaques progressed less in FH heterozygotes than in non-FH subjects, in both instances despite FH patients having higher LDL cholesterol levels on treatment. These findings suggest that, compared with non-FH subjects, atherosclerotic lesions in FH heterozygotes may be hyper-responsive to LDL-lowering therapy, whereas treatment of homozygous FH remains a major challenge. [ABSTRACT FROM AUTHOR]

The objective of this study was to review available health economic evaluations of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. These drugs reduce low-density lipid cholesterol levels and cardiovascular risk, but their cost effectiveness has been questioned. We searched Medline and Embase for economic evaluations in any language at any time. Studies were included if they analysed any PCSK9 inhibitor compared with either statin alone or in combination with ezetimibe or any other therapy considered standard prior to the introduction of PCSK9 inhibitors. We found ten full health economic evaluations of PCSK9 inhibitors, two from Europe and eight from the United States (US). Six of the eight from the US were from two different consortia that analysed PCSK9 inhibitors at different stages through the development of evidence. All studies generally reported incremental cost-effectiveness ratios above suggested thresholds for cost effectiveness, except one study from Spain. The results of this review indicate that PCSK9 inhibitors in general are not cost effective at the current prices, but lower prices may change the results. [ABSTRACT FROM AUTHOR]

Purpose Watermelon (Citrullus lanatus) fruit and its rind are known to contain phytochemicals that may have health benefits. The aim of this paper is to investigate the potential hypocholesterolemic effect of watermelon fruit rind (WR) using rats who are fed a high-cholesterol diet.Design/methodology/approach Rats were divided into six groups and fed diets for eight weeks containing normal control diet or normal control diet with either 1% cholesterol, 5% WR, 10% WR, 1% cholesterol + 5% WR or 1% cholesterol + 10% WR. Triglycerides, total cholesterol and lipoprotein levels in serum and liver samples were determined, and histopathological examination of liver tissues was carried out.Findings Diets containing 1% cholesterol led to hypercholesterolemia, characterized by increased levels of total cholesterol and low-density lipoproteins in rat serum and liver samples. Incorporation of 10% WR into the diet of the otherwise hypercholesterolemic rats led to significant reduction in serum levels of total cholesterol (from 266.2 to 222.7 mg/dL) and low-density lipoproteins (from 159.5 to 94.4 mg/dL). In addition, these rats also exhibited improvements in hepatic tissue structure compared to the hypercholesterolemic rats.Originality/value These results support the potential use of WR as a hypocholesterolemic agent. Further research is needed to ascertain the hypocholesterolemic effect of WR in human. [ABSTRACT FROM AUTHOR]

High-density lipoprotein (HDL) is a key regulator of lipid homeostasis through its native roles like reverse cholesterol transport. The reconstitution of this natural nanoparticle (NP) has become a nexus between nanomedicine and multi-disease therapies, for which a major portion of HDL functionality is attributed to its primary scaffolding protein, apolipoprotein A1 (apoA1). ApoA1-mimetic peptides were formulated as cost-effective alternatives to apoA1-based therapies; reverse-4F (r4F) is one such peptide used as part of a nanoparticle platform. While similarities between r4F- and apoA1-based HDL-mimetic nanoparticles have been identified, key functional differences native to HDL have remained undetected. In the present study, we executed a multidisciplinary approach to uncover these differences by exploring the form, function, and medical applicability of engineered HDL-mimetic NPs (eHNPs) made from r4F (eHNP-r4F) and from apoA1 (eHNP-A1). Comparative analyses of the eHNPs through computational molecular dynamics (MD), advanced microfluidic NP synthesis and screening technologies, and in vivo animal model studies extracted distinguishable eHNP characteristics: the eHNPs share identical structural and compositional characteristics with distinct differences in NP stability and organization; eHNP-A1 could more significantly stimulate anti-inflammatory responses characteristic of the scavenger receptor class B type 1 (SR-B1) mediated pathways; and eHNP-A1 could outperform eHNP-r4F in the delivery of a model hydrophobic drug to an in vivo tumor. The biomimetic microfluidic technologies and MD simulations uniquely enabled our comparative analysis through which we determined that while eHNP-r4F is a capable NP with properties mimicking natural eHNP-A1, challenges remain in reconstituting the full functionality of NPs naturally derived from humans. [ABSTRACT FROM AUTHOR]

Abstract The present study explored the effect of cholesterol on the immunity and inflammation response in the immune organs (head kidney, spleen and skin) of young grass carp ( Ctenopharyngodon idella ) fed graded levels of dietary cholesterol (0.041–1.526%) for 60 days and then infected with Aeromonas hydrophila for 14 days. The results showed that low levels of cholesterol (1) depressed the innate immune components [lysozyme (LZ), acid phosphatase (ACP), complements and antimicrobial peptides] and adaptive immune component [immunoglobulin M (IgM)], (2) up-regulated the mRNA levels of pro-inflammatory cytokines [interleukin 1β (IL-1β), IL-6, IL-8, IL-12p35, IL-12p40, IL-15, IL-17D, tumor necrosis factor α (TNF-α) and interferon γ2 (IFN-γ2)], partly due to the activated nuclear factor kappa B (NF-κB) signalling, and (3) down-regulated the mRNA levels of anti-inflammatory cytokines [IL-4/13B, IL-10, IL-11, transforming growth factor (TGF)-β1 and TGF-β2], partly due to the suppression of target of rapamycin (TOR) signalling in the immune organs of young grass carp. Interestingly, dietary cholesterol had no influences on the IκB kinase α (IKKα) and IL-4/13A mRNA levels in the head kidney, spleen and skin, the IL-1β and IL-12p40 mRNA levels in the spleen and skin, or the β-defensin-1 mRNA level in the skin of young grass carp. Additionally, low levels of cholesterol increased the skin haemorrhage and lesion morbidity. In summary, low levels of cholesterol impaired immunity by depressing the innate and adaptive immune components, and low levels of cholesterol aggravated the inflammation response via up-regulating the expression of pro-inflammatory cytokines as well as down-regulating the expression of anti-inflammatory cytokines partly through the modulation of NF-κB and TOR signalling in the immune organs of fish. Similar to the low level of cholesterol, the excess level of dietary cholesterol impaired immunity and aggravated inflammation response in the immune organs of fish. Finally, based on the percent weight gain (PWG), the ability against skin haemorrhage and lesions as well as the LZ activity in the head kidney and the ACP activity in the spleen, the optimal dietary cholesterol levels for young grass carp were estimated as 0.721, 0.826, 0.802 and 0.772% diet, respectively. Highlights • Inadequate cholesterol depressed innate and adaptive immune components in fish. • Inadequate cholesterol aggravated fish inflammation response involving cytokines. • Dietary cholesterol regulated NF-κB and TOR signaling in fish immune organs. • Excess cholesterol impaired immunity and aggravated inflammation response in fish. [ABSTRACT FROM AUTHOR]

Elevation of circulating levels of blood cholesterol, especially LDL cholesterol, and/or the decrease of HDL cholesterol levels have long been recognized as primary risk factors for developing atherosclerosis that leads to cardiovascular and cerebrovascular disease. Hypertriglyceridemia is an independent risk factor that is known to contribute to the development of atherosclerosis. Thus, various interventional efforts aimed at reducing hypercholesterolemia and hypertriglyceridemia have been practiced clinically for decades to reduce morbidity and mortality risk associated with deleterious cardiovascular and cerebrovascular events. As such, many drugs have been developed and clinically used to treat hypocholesteremia and/or hypertriglyceridemia; however, dietary approaches including supplements along with changes in nutrition and lifestyle have become increasingly attractive and acceptable methods used to control borderline or moderately increased levels of blood cholesterol and triacylglycerols. In this regard, the use of a plant/herbal bioactive compound, berberine (BBR), has recently been studied extensively in terms of its efficacy as well as its mechanisms of action and safety as an alternative intervention that beneficially modulates blood lipids. The aim of this review is to provide a comprehensive update on BBR research, new concepts and directions in terms of product development and current challenges, and future prospects of using BBR to manage diseases and complications associated with dyslipidemia. [ABSTRACT FROM AUTHOR]

Le cholestérol et les traitements par statines font l'objet d'une controverse intense. L'athérosclérose est une maladie largement étudiée mais aussi complexe et toujours largement incomprise. Le cholestérol est un facteur de risque cardiovasculaire majeur dans le cas des hypercholestérolémies familiales et réduire son taux est crucial dans ces situations. En revanche réduire la cholestérolémie chez les sujets normocholestérolémiques permet de retarder les événements cardiovasculaires seulement de quelques semaines en moyenne. Les gains modestes en termes d'espérance de vie médiane ou de nombre de sujets à traiter obtenus avec un traitement par statines devraient donc susciter des études complémentaires afin d'identifier et de traiter les patients qui ont le plus de chance de tirer bénéfice des statines et, à l'inverse, d'identifier les patients qui ne bénéficieraient pas de cette thérapeutique et/ou des fortes doses de statines. L'approche actuelle de type "one size fits all" issue des essais randomisés et des recommandations n'est probablement pas l'approche future de la médecine personnalisée dite de précision. [ABSTRACT FROM AUTHOR]

Aims Disruption of cholesterol homeostasis has been identified as a major factor in the pathogenesis of atherosclerosis, myocardial infarction, and strokes. Long noncoding RNAs (lncRNAs) have emerged as critical players in cellular cholesterol metabolism, but their functions are still largely unknown. Materials and methods C57BL6/j mice were fed with high cholesterol diet (containing 4% cholesterol) or chow diet. Adenoviruses-lncARSR and lncARSR shRNA were used to overexpress or knockdown lncARSR expression. Key findings The expression of lncARSR were increased both in patients with hypercholesterolemia and mice with high cholesterol diet feeding. Overexpression of lncARSR in mice resulted in elevated lipid levels in both serum and liver fragments. However, knockdown of lncARSR in mice fed with high cholesterol diet showed decreased lipid levels in serum and liver fragments compared with control mice. Furthermore, we found that the expression of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol synthesis was increased with lncARSR overexpression, which was accompanied with the increase of hepatic de novo cholesterol synthesis rate. Mechanistically, we found that lncARSR increased the expression of mature SREBP-2, which is a primary transcription factor of HMGCR. And lncARSR activated the PI3K/Akt pathway. When PI3K/Akt pathway was blocked by LY294002, the inhibitor of PI3K, the effect of lncARSR on SREBP-2 and HMGCR disappeared. Significance Our data indicated upregulated lncARSR promotes hepatic cholesterol biosynthesis via modulating Akt/SREBP-2/HMGCR pathway, and implied that lncARSR may serve as a therapeutic target for cholesterol disorder. [ABSTRACT FROM AUTHOR]

Dietary fiber (DF) has drawn the attention of researchers due to its significant health benefits. Over the past decade greater DF materials from fruits and vegetables are being introduced in the market because of the presence of associated bioactive compounds and balanced compositions. The physicochemical and functional properties of DFs always depend on the food sources, extraction methods and structure of DF. Garlic bulb is consumed worldwide because of its widespread medicinal and nutritional value. During harvesting period, garlic bulb yields a considerable amount of straw which is simply thrown or disposed, causing a severe environmental problem. Garlic straw, with similar compounds to garlic bulb, might be used as a novel source of functional DF. Composition analysis reveals garlic straw consists of 7.15% soluble dietary fiber (SDF) and 72.20% insoluble dietary fiber (IDF), which exhibit different physiological effects on human health. The health effects exhibited by IDF are often not as good as that of SDF due to their different physicochemical and functional properties. Therefore, the aim of this study was to improve the functional properties of IDF from garlic straw with ultrasonic processing technology. IDF was put into a 500 mL beaker and dispersed with 300 mL deionized water. The beaker containing the sample was placed in a thermostatic water bath at initial temperatures of 25℃ for 10 min. And then the mixture was sonicated in ultrasound processor with different liquid-sample ratios, ultrasonic powers and ultrasonic time. After the pretreatment, the mixture was stored at -20℃ and freeze-dried for later analysis. The optimum ultrasonic conditions were obtained based on the responses of glucose absorption capacity from single factor experiments and response surface methodology. The functional properties including cholesterol binding capacity, water holding capacity, oil holding capacity and water swelling capacity were determined. Scanning electron microscope (SEM) and Fourier transformed infrared spectroscopy (FTIR) were used to analyze the microstructure of IDF. Results suggest that liquid-sample ratio of 30:1, ultrasonic power of 700 W and ultrasonic time of 40 min were considered as the optimum ultrasonic conditions for preparation of IDF with good glucose absorption capacity. Under these conditions, the glucose absorption capacity and cholesterol binding capacity were increased by 12.8% and 45.0% compared to those without ultrasound treatment (P<0.05). Ultrasonic-treated IDF exhibited better color, functional and physicochemical properties than untreated IDF with significant difference (P<0.05). FTIR of control and ultrasonic-treated IDF was basically the same. Structural analysis from SEM indicated that ultrasonic treatment destroyed the microstructure of IDF from garlic straw. Findings from structural analysis revealed that the porosity and surface area of IDF were effectively improved by ultrasound, which proved to enhance functional and physicochemical properties of modified IDF. The positive effect of ultrasound may be useful for functional modification and utilization of DF from garlic straw. [ABSTRACT FROM AUTHOR]

Intracellular cholesterol transport proteins move cholesterol to different subcellular compartments and thereby regulate its final metabolic fate. In hepatocytes, for example, delivery of high-density lipoprotein (HDL)-associated cholesterol for bile acid synthesis or secretion into bile facilitates cholesterol elimination from the body (anti-atherogenic effect), whereas delivery for esterification and subsequent incorporation into apolipoprotein B-containing atherogenic lipoproteins (e.g. very-low-density lipoprotein (VLDL)) enhances cholesterol secretion into the systemic circulation (pro-atherogenic effect). Intracellular cholesterol transport proteins such as sterol carrier protein-2 (SCP2) should, therefore, play a role in regulating these pro- or anti-atherosclerotic processes. Here, we sought to evaluate the effects of SCP2 deficiency on the development of diet-induced atherosclerosis. We generated LDLR-/-/ mice deficient in SCP2/SCPx (LS) and examined the effects of this deficiency on Western diet-induced atherosclerosis. SCP2/ SCPx deficiency attenuated atherosclerosis in LS mice by>80% and significantly reduced plasma cholesterol and triglyceride levels. Investigation of the likely underlying mechanisms revealed a significant reduction in intestinal cholesterol absorption (given as an oral gavage) in SCP2/SCPx-deficient mice. Consistently, siRNA-mediated knockdown of SCP2 in intestinal cells significantly reduced cholesterol uptake. Furthermore, hepatic triglyceride/VLDL secretion from the liver or hepatocytes isolated from SCP2/SCPx-deficient mice was significantly reduced. These results indicate an important regulatory role for SCP2 deficiency in attenuating diet-induced atherosclerosis by limiting intestinal cholesterol absorption and decreasing hepatic triglyceride/VLDL secretion. These findings suggest targeted inhibition of SCP2 as a potential therapeutic strategy to reduce Western diet-induced dyslipidemia and atherosclerosis. [ABSTRACT FROM AUTHOR]

Aims: Type 2 diabetes (T2D) is a complex metabolic disease with high incidence throughout the world. Dyslipidemia is the leading cause of atherosclerotic cardiovascular diseases (ASCVD) in T2D patients. hsa-miR-33 (miR-33) serves as a regulator in lipid metabolism. We hypothesized that blood miR-33 associates with serum lipids in T2D patients at high risk of ASCVD events.Methods: We developed a branched rolling circle amplification (B-RCA) method and assessed its sensitivity and specificity with miR-33a/b standards by traditional TaqMan assay. Circulating miR-33a/b level was then determined with B-RCA in 30 T2D patients at high risk for developing ASCVD and 33 healthy controls. Pearson correlation coefficient was used to evaluate the correlation between circulating miR-33a/b and serum cholesterol.Results: Compared with TaqMan assay, B-RCA method showed a similar specificity and a 100-fold higher sensitivity for miR-33a detection. Circulating miR-33a/b level is positively correlated with serum total cholesterol (TC) (r = 0.364, p = 0.048) and low-density lipoprotein cholesterol (LDL-C) (r = 0.383, p = 0.037) in T2D patients at high risk for developing ASCVD.Conclusions: Our B-RCA method provided an alternative strategy with specificity and high sensitivity for circulating miRNAs detection, and the results demonstrated that miR-33a/b might play an important role in cholesterol regulation. [ABSTRACT FROM AUTHOR]

Abstract: Egg yolk was replaced with sesame–peanut meal milk in mayonnaise in the levels of 0, 25%, 50%, 75%, and 100%. The pH was significantly decreased by increasing the percentage of replacement in all three kinds of replacement (p < .05). However, over the whole period, no significant difference was observed in the acidity. The mayonnaise samples, except for the replacements of 50%, were desirable in terms of physical and thermal stability. A significant decrease was seen in lightness (L*) and yellowness (b*) of the samples as a result of an increase in the percentage of replacements (p < .05). In the power law model, the flowing index amount (n) of all samples was in the domain between zero and one, which served as evidence for pseudoplastic behavior (dilatant with shear) of mayonnaise samples. The positive results are employing suitably the sesame–peanut meal milk instead of egg yolk, decreasing the cholesterol of mayonnaise and increasing its nutritional value, proposing mayonnaise factories to make use of the meal of the oil extraction factory as emulsifier, which lead to a decrease in overall costs of producing these products. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: Cholesterol granuloma is a benign condition that can be misdiagnosed as breast cancer on mammographic and ultrasound imaging. A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast was imaged with ultrasound elastography and magnetic resonance imaging (MRI) methods, including T1-weighted dynamic contrast-enhanced MRI (DCE-MRI), before biopsy and histopathology. Case Report: A 52-year-old woman, with a previous history of intraduct papillomas in both breasts, underwent six-monthly follow-up breast imaging. The most recent breast mammogram showed a progressively enlarging oval mass in the upper inner quadrant (UIQ) of the left breast, and an adjacent irregular mass with microcalcifications. Virtual Touch IQ (VTIQ) shear wave elastography was used with ultrasound of the breast lesions. T1-weighted fat saturation (T1WFS) MRI, T2-weighted short-tau inversion recovery (STIR) MRI, and T1-weighted DCE-MRI were used to image the left breast. T1-weighted DCE-MRI showed that the oval lesion had a high T1-weighted signal and mild progressive enhancement, with a Type I (benign) time-signal intensity curve; the second, irregular, mass showed rapid, intense enhancement with a washout pattern or Type III (malignant) time-signal intensity curve. Histopathology confirmed that the oval mass was a cholesterol granuloma, and the irregular mass was an invasive ductal carcinoma. Conclusions: A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast, showed that ultrasound with shear wave elastography and T1-weighted DCE-MRI could distinguish between cholesterol granuloma and invasive ductal carcinoma. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia (FH) and other extreme elevations in low-density lipoprotein cholesterol significantly increase the risk of atherosclerotic cardiovascular disease; however, recent data suggest that prescription rates for statins remain low in these patients. National rates of screening, awareness, and treatment with statins among individuals with FH or severe dyslipidemia are unknown.Methods: Data from the 1999 to 2014 National Health and Nutrition Examination Survey were used to estimate prevalence rates of self-reported screening, awareness, and statin therapy among US adults (n=42 471 weighted to represent 212 million US adults) with FH (defined using the Dutch Lipid Clinic criteria) and with severe dyslipidemia (defined as low-density lipoprotein cholesterol levels ≥190 mg/dL). Logistic regression was used to identify sociodemographic and clinical correlates of hypercholesterolemia awareness and statin therapy.Results: The estimated US prevalence of definite/probable FH was 0.47% (standard error, 0.03%) and of severe dyslipidemia was 6.6% (standard error, 0.2%). The frequency of cholesterol screening and awareness was high (>80%) among adults with definite/probable FH or severe dyslipidemia; however, statin use was uniformly low (52.3% [standard error, 8.2%] of adults with definite/probable FH and 37.6% [standard error, 1.2%] of adults with severe dyslipidemia). Only 30.3% of patients with definite/probable FH on statins were taking a high-intensity statin. The prevalence of statin use in adults with severe dyslipidemia increased over time (from 29.4% to 47.7%) but not faster than trends in the general population (from 5.7% to 17.6%). Older age, health insurance status, having a usual source of care, diabetes mellitus, hypertension, and having a personal history of early atherosclerotic cardiovascular disease were associated with higher statin use.Conclusions: Despite the high prevalence of cholesterol screening and awareness, only ≈50% of adults with FH are on statin therapy, with even fewer prescribed a high-intensity statin; young and uninsured patients are at the highest risk for lack of screening and for undertreatment. This study highlights an imperative to improve the frequency of cholesterol screening and statin prescription rates to better identify and treat this high-risk population. Additional studies are needed to better understand how to close these gaps in screening and treatment. [ABSTRACT FROM AUTHOR]

Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear.Objective: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity.Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure.Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively).Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012. [ABSTRACT FROM AUTHOR]

Cholesterol is an important regulator of cell signaling, both through direct impacts on cell membranes and through oxy-metabolites that activate specific receptors (steroids, hydroxy-cholesterols, bile acids). Cholesterol moves slowly through and between cell membranes with the assistance of specific binding proteins and transfer processes. The prototype cholesterol regulator is the Steroidogenesis Acute Regulatory (STAR), which moves cholesterol into mitochondria, where steroid synthesis is initiated by cytochrome P450 11A1 in multiple endocrine cell types. CYP27A1 generates hydroxyl cholesterol metabolites that activate LXR nuclear receptors to control cholesterol homeostatic and transport mechanisms. LXR regulation of cholesterol transport and storage as cholesterol ester droplets is shared by both steroid-producing cells and macrophage. This cholesterol signaling which is crucial to brain neuron regulation by astrocytes and microglial macrophage, is mediated by ApoE and is sensitive to disruption by β-amyloid plaques. sm-FISH delivers appreciable insights into signaling in single cells, by resolving single RNA molecules as mRNA and by quantifying pre-mRNA at gene loci. sm-FISH has been applied to problems in physiology, embryo development and cancer biology, where single cell features have critical impacts. sm-FISH identifies novel features of STAR transcription in adrenal and testis cells, including asymmetric expression at individual gene loci, delayed splicing and 1:1 association of mRNA with mitochondria. This may represent a functional unit for the translation-dependent cholesterol transfer directed by STAR, which integrates into mitochondrial fusion dynamics. Similar cholesterol dynamics repeat with different players in the cycling of cholesterol between astrocytes and neurons in the brain, which may be abnormal in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Many studies have reported the causes of obese metabolic syndrome (MS); however, the causes of nonobese MS (NMS) remain unknown. In this study, we demonstrated that inflamed dysfunctional adipose tissue plays a crucial role in cholesterol-induced NMS. Control (C), high cholesterol (HC) and HC with 10% fructose in drinking water (HCF) diets were fed to Sprague-Dawley rats for 12 weeks. After 12 weeks, the body weights of the C- and HC-fed rats were comparable, but the weights of the HCF-fed rats were relatively low. Cholesterol caused metabolic problems such as high blood pressure, hypercholesterolemia and hypoinsulinemia. The HCF-fed rats exhibited whole-body insulin resistance with low circulating high-density lipoprotein levels. Increases in the tumor necrosis factor α level in the plasma, the number of CD68+ macrophages and the free nuclear factor-κB level in gonadal white adipose tissue (gWAT) resulted in local inflammation, which appeared as inflamed dysfunctional gWAT. Reduced superoxide dismutases (SODs) deteriorate natural antioxidant defense systems and induce reactive oxygen species in gWAT. Dysregulation of plasma levels of catecholamine, adipokines (leptin and adiponectin), hormone-sensitive lipase and perilipin in cholesterol-induced inflamed adipose tissue contributed to increased lipolysis and increased circulating nonesterified fatty acids. Cholesterol activated inflammation, lipolysis and cell death in 3T3-L1 adipocytes. Moreover, Chol-3T3-CM reduced the population of M2-type Raw264.7 macrophages, indicating that the macrophage polarization is mediated by cholesterol. Together, our findings indicate that inflamed dysfunctional adipocytes are critical in NMS, supporting the development of anti-inflammatory agents as potential therapeutic drugs for treating NMS. [ABSTRACT FROM AUTHOR]

An important feature of the intestinal microbiota, particularly in the case of administered probiotic microorganisms, is their resistance to conditions in the gastrointestinal tract, particularly tolerance to and growth in the presence of bile salts. Bacteria can use several defence mechanisms against bile, including special transport mechanisms, the synthesis of various types of surface proteins and fatty acids or the production of exopolysaccharides. The ability to enzymatically hydrolyse bile salts occurs in a variety of bacteria. Choloylglycine hydrolase (EC 3.5.1.24), a bile salt hydrolase, is a constitutive intracellular enzyme responsible for the hydrolysis of an amide bond between glycine or taurine and the steroid nucleus of bile acids. Its presence was demonstrated in specific microorganisms from several bacterial genera ( Lactobacillus spp., Bifidobacterium spp., Clostridium spp., Bacteroides spp.). Occurrence and gene arrangement encoding this enzyme are highly variable in probiotic microorganisms. Bile salt hydrolase activity may provide the possibility to use the released amino acids by bacteria as sources of carbon and nitrogen, to facilitate detoxification of bile or to support the incorporation of cholesterol into the cell wall. Deconjugation of bile salts may be directly related to a lowering of serum cholesterol levels, from which conjugated bile salts are synthesized de novo . Furthermore, the ability of microorganisms to assimilate or to bind ingested cholesterol to the cell wall or to eliminate it by co-precipitation with released cholic acid was also documented. Some intestinal microflora produce cholesterol reductase that catalyses the conversion of cholesterol to insoluble coprostanol, which is subsequently excreted in faeces, thereby also reducing the amount of exogenous cholesterol. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia is a well-established risk factor for coronary heart disease, but the association between cholesterol level change and mortality is not fully understood. We aimed to investigate the association of 2 year (2002–2003 to 2004–2005) change in cholesterol with all-cause and cause-specific mortality in a population-based cohort study. Methods and findings: The study population consisted of 269,391 participants aged more than 40 years who were free of myocardial infarction, stroke and cancer using the Korean National Health Insurance Service—National Health Screening Cohort. Cholesterol levels were classified into 1st, 2nd and 3rd tertiles during each of the first and second health examinations, respectively. The participants were followed-up for all-cause and cause-specific mortality from 1 January 2006 to 31 December 2013. Compared to participants who stayed within the 2nd tertile group for cholesterol during both the first and second examinations, participants who became or maintained cholesterol levels to the 1st tertile during the second examination had increased risk of all-cause mortality [adjusted hazard ratio (aHR) with 95% confidence interval (95% CI) = 1.28 (1.18–1.38) in 1st/1st, 1.16 (1.07–1.26) in 2nd/1st and 1.47 (1.32–1.64) in 3rd/1st tertile levels, respectively]. In addition, increased or persistent high cholesterol levels to the 3rd tertile was associated with elevated risk for all-cause mortality [aHR (95% CI) = 1.10 (1.01–1.20) in 1st/2nd, 1.16(1.03–1.31) in 1st/3rd and 1.15(1.05–1.25) in 3rd/3rd tertile levels]. Conclusions: Changes in cholesterol levels in either direction to low cholesterol or persistently low cholesterol levels were associated with higher risk of mortality. Particularly, spontaneous decline in cholesterol levels may be a marker for worsening health conditions. [ABSTRACT FROM AUTHOR]

Spontaneous insertion of membrane proteins into liposomes formed from Escherichia coli polar phospholipids is blocked by diacylglycerol (DAG) at a physiological level. We found that cholesterol also blocks this spontaneous insertion, although a much larger amount is necessary for sufficient blockage. Reversely, sphingomyelin enhanced the spontaneous insertion. DAG at a physiological level was found not to block spontaneous insertion into liposomes formed from phosphatidylcholine (PC), while non-physiologically high concentrations of DAG reduced it. On the other hand, cholesterol blocked the spontaneous insertion into PC liposomes at a physiological level, explaining that both PC and cholesterol are absent in E. coli. While sphingomyelin did not enhance spontaneous insertion into PC liposomes, the effect of cholesterol on blockage of spontaneous insertion was dominant over that of sphingomyelin, suggesting that cholesterol functions as a blocker of disordered spontaneous insertion in eukaryotic cells. Lower amount of cholesterol was necessary to block spontaneous insertion into ER-mimic liposomes, explaining that ER membranes contain less amount of cholesterol. These results also explain that cholesterol, but not DAG, is involved in blockage of spontaneous insertion in eukaryotic cells, since DAG plays an important role as a second messenger in signal transduction. [ABSTRACT FROM AUTHOR]

Cholesterol is a major sterol in crustaceans that occurs in all cells and in the hemolymph, either in free form or combined with fatty acids. Unlike vertebrates, shrimps and other crustaceans are incapable of de novo synthesis of cholesterol; therefore, dietary cholesterol is essential for their growth and survival. Their requirement, however, is often species-specific and may also depend on the dietary protein and lipid sources. Dietary lipid sources can include the presence of phytosterols and phospholipids, which may have a cholesterol sparing effect in some species. On the other hand, compounds found within some fishmeal alternatives may disrupt cholesterol utilization. Understanding these relationships is important because cholesterol is essential for the synthesis of ecdysteroids and sesquiterpenoids, which are a class of hormones that regulate moulting and reproduction in crustaceans. The biosynthetic pathway of these hormones is not completely understood in crustaceans. When knowledge gaps exist, available information from a better-studied animal group (the insect), is extrapolated to produce a hypothetical model of putative ecdysteroid synthesis in crustaceans. The key steps in cholesterol metabolism, including digestion, absorption, and transportation are highlighted. There is also a focus on various pathways involving candidate genes (encoding enzymes) linking cholesterol metabolism and moulting. Considering the relatively high cost of cholesterol, a better understanding of factors influencing dietary cholesterol requirements in crustaceans and role this plays in lipid metabolism may facilitate more cost-effective feed formulations. [ABSTRACT FROM AUTHOR]

Abstract: Cholesterol affects cancer progression, and acetyl‐CoA is the primary cholesterogenesis substrate. The previous work has defined cholesterol bioflux via lipoprotein/receptor route is the gastric cancer (GCa) prognosis biosignature. The prognosis importance of acetyl‐CoA to cholesterogenesis (mevalonate pathway) in GCa is yet to be defined. Using Kaplan–Meier Plotter web‐based gene survival analyzer and The Cancer Genome Atlas (TCGA)‐database analyzed with DBdriver.v2 platform, we revealed acetyl‐CoA production and the mevalonate pathway are associated with GCa prognosis. We found mitochondrial‐derived acetyl‐CoA contributing enzymes (acyl‐coA synthetase super‐family 3; ACSS3) is the GCa progression confounder. Interestingly, it is not HMGCR (the committee enzyme of mevalonate pathway), but lower mevalonate pathway enzymes (e.g., MVK, LSS, DHCR14A1, SC4MOL, HSD17B7, SC5D) promote GCa patients 5‐years overall survival in a differential level. Advanced analyses found ACSS3 is prognosis biosignatures for multiple GCa disease conditions. This report uncovered a higher expression of ACSS3 in tumor comparing to normal parental lesions, which implicates a targeting value for GCa therapy. While knockdown ACSS3 could suppress growth and invasion of GCa cells, of which even more impactful under starvation condition. This is the first report, surprisingly, revealed ACSS3 as important cancer prognosis biomarker. Targeting ACSS3 could be a novel therapeutic strategy for cancer, in this case, GCa. [ABSTRACT FROM AUTHOR]

The role of cholesterol in bilayer and monolayer lipid membranes has been of great interest. On the biophysical front, cholesterol significantly increases the order of the lipid packing, lowers the membrane permeability, and maintains membrane fluidity by forming liquid-ordered-phase lipid rafts. However, direct observation of any influence on membrane chemistry related to these cholesterol-induced physical properties has been absent. Here we report that the addition of 30 mol % cholesterol to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) monolayers at the air-water interface greatly reduces the oxidation and ester linkage cleavage chemistries initiated by potent chemicals such as OH radicals and HCl vapor, respectively. These results shed light on the indispensable chemoprotective function of cholesterol in lipid membranes. Another significant finding is that OH oxidation of unsaturated lipids generates Criegee intermediate, which is an important radical involved in many atmospheric processes. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of b-site APP cleaving enzyme-1 (BACE1) and receptor for advanced glycation end products (RAGE), and increase the expression levels of low density lipoprotein receptorrelated protein 1 (LRP-1) and insulin degrading enzyme (IDE). In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA) and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD. [ABSTRACT FROM AUTHOR]

Background Vitamin D deficiency is a prevalent and important global health problem. Because of its role in growth and development, vitamin D status is likely to be particularly important in adolescent girls. Here, we explored the effects of high-dose vitamin D supplementation on cardio-metabolic risk factors. Methods We have examined the effects of vitamin D supplementation on cardio-metabolic risk factors in 988 healthy adolescent girls in Iran. Fasting blood samples and anthropometric measurements were obtained at baseline and after supplementation with high-dose vitamin D. All individuals took a capsule of 50,000 IU vitamin D/week for nine weeks. The study was completed by 940 participants. Results The prevalence of vitamin D deficiency was 90% at baseline, reducing to 16.3% after vitamin D supplementation. Vitamin supplementation was associated with a significant increase in serum concentrations of 25 (OH) vitamin D and calcium. There were significant reductions in diastolic blood pressure, heart rate, waist circumference and serum fasting blood glucose, total- and low-density lipoprotein-cholesterol after the nine-week period on vitamin D treatment, but no significant effects were observed on body mass index, systolic blood pressure or serum high-density lipoprotein cholesterol and triglyceride. Conclusion Vitamin D supplementation had beneficial effects on cardio-metabolic profile in adolescent girls. [ABSTRACT FROM AUTHOR]

The effect of cholesterol (CHOL) content on the permeability and fluidity of dipalmitoylphosphatidylcholine (DPPC) liposome membrane was investigated. Liposomes encapsulating sulforhodamine B (SRB), a fluorescent dye, were prepared by reverse phase evaporation technique (REV) at various DPPC:CHOL molar ratios (from 100:0 to 100:100). The release kinetics of SRB was studied during 48 h in buffer (pH 7.4) containing NaCl at 37 °C. The DPPC:CHOL formulations were also characterized for their size, polydispersity index and morphology. Increasing CHOL concentration induced an increase in the mean liposomes size accompanying with a shape transition from irregular to nanosized, regular and spherical vesicles. The release kinetics of SRB showed a biphasic pattern; the release data was then analyzed using different mathematical models. On the overall, the SRB release was governed by a non-Fickian diffusion during the first period (0–10 h) while it followed a Fickian diffusion between 10 and 48 h. Changes in DPPC liposome membrane fluidity of various batches (CHOL% 0, 10, 20, 30 and 100) were monitored by using 5- and 16 doxyl stearic acids (DSA) as spin labels. CHOL induced a decrease in the bilayer fluidity. Concisely, CHOL represents a critical component in modulating the release of hydrophilic molecules from lipid vesicles. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether plasma cholesterol concentrations in dogs with sepsis is associated with morbidity or in‐hospital mortality. Design: Retrospective cohort study from 2005–2015. Setting: Two private referral centers. Animals: Fifty‐one dogs diagnosed with sepsis. Interventions: None. Measurements and Main Results: Dogs were classified as septic if they displayed ≥2 criteria of the systemic inflammatory response syndrome in conjunction with a documented underlying infectious cause. Dogs were excluded if they had been diagnosed previously with any concurrent illness reported to alter plasma cholesterol concentrations. Plasma cholesterol concentrations at the time of sepsis diagnosis were statistically analyzed for association with morbidity, as measured by the presence of organ dysfunction, the number of dysfunctional organs, duration of hospitalization, cost of hospitalization, and in‐hospital mortality. Twenty‐eight (55%) dogs survived to discharge, 15 (29%) were euthanized during hospitalization, and 8 (16%) died despite treatment. While median cholesterol concentrations were significantly different when comparing survivors to discharge versus nonsurvivors who died naturally despite treatment (P = 0.0245), they were not significantly different when comparing survivors to all nonsurvivors (P = 0.1821). Receiver operating characteristic curve analysis showed a cholesterol cutoff of 4.5 mmol/L (174 mg/dL) with a sensitivity of 75% and a specificity of 50% for predicting in‐hospital mortality. For surviving dogs, plasma cholesterol concentrations were not associated with increased length of hospital stay. Number of dysfunctional organs and plasma cholesterol concentration were the 2 most significant individual predictors for survival, and when incorporated into a multivariate logistic regression model used for prediction, the model yielded a sensitivity of 94% and specificity of 63%. Conclusion: Plasma cholesterol concentration can provide prognostic information in dogs with sepsis. Further prospective studies investigating the role of cholesterol in sepsis are needed. [ABSTRACT FROM AUTHOR]

Cholesterol plays an important role in regulating the properties of phospholipid bilayers and many mechanisms have been proposed to explain why cholesterol is so ubiquitous within biological membranes of animals. Here we present the results of studies on the effect of cholesterol on the electrical/dielectric properties of lipid membranes tethered to a solid substrate. These tethered bilayer lipid membranes tBLM were formed on a commercially available chemically modified gold substrate. These lipid bilayers are very robust. Very high-resolution electrical impedance spectroscopy (EIS) was used to determine the dielectric structure of the lipid bilayers and associated interfaces. The EIS data allowed the dielectric substructure of the lipid bilayers to be determined. The results showed that when cholesterol was present in the tethered membranes at a concentration of 10% (mol/mol); the thickness of the tBLMs increased and the membrane conductance decreased. However, when cholesterol was present in the tethered membrane at more than 30% (mol/mol) the effect of cholesterol was dramatically different; the membranes then became thinner and possessed a much larger electrical conductance. The EIS allowed a distinction to be made between a hydrophobic region in the center of the bilayer and another hydrophobic region further out towards the polar head region, in addition to the polar head region itself. Cholesterol was found to have the largest effect on the inner, hydrophobic region, although the outer hydrophobic region was also affected. [ABSTRACT FROM AUTHOR]