Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Biochemistry and transcriptome analysis reveal condensed tannins alleviate liver injury induced by regulating cholesterol metabolism pathway

Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.

Cholesterol and Sericin as First Aid for Damaged Cells

Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection and communication. These cell membranes must be intact and functionally active for cell survival and biological functioning. Compromised damage repair mechanisms usually result in impaired cellular homeostasis, leading to early or late problems. Chronic myopathies, certain myocardial diseases, aging, and acute or chronic neurodegenerative diseases (like Parkinson and Alzheimer) are directly related to cell membrane damage. This study examined the effect of a cholesterol-loaded nanoparticle (methyl-beta cyclodextrin) or the silk protein sericin on cell membrane and DNA integrity and cell viability in an in vitro cell damage model (frozen-thawed rabbit sperm cells). The cells were stored in liquid nitrogen (-196°C), thawed in small batches, and treated with cholesterol-loaded cyclodextrin or sericin before incubation at 35°C for 4 hours. Cell membrane integrity, DNA damage, and viability rates were assessed immediately after thawing and after the incubation period. The administration of sericin and cholesterol in a cell damage model increased cell survival and reduced DNA damage over a 4-hour post-thaw incubation period, suggesting their potential use as a “first aid” intervention at the cellular level.

Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

Inhibitory effect of procyanidin B2 and tannin acid on cholesterol esterase and their synergistic effect with orlistat

This study was aimed to analyze the effect of procyanidin B2(PC)and tannin acid(TA)on the activities of cholesterol esterase(CEase)and the inhibitory mechanisms of enzymatic activity.The interaction mechanisms were investigated by enzymatic kinetics,multi-spectroscopy methods,thermodynamics analysis,molecular docking,and dynamic simulations.PC and TA could bind with CEase and inhibit the activity of enzyme in a mixed-competitive manner and non-competitive manner,which was verified by molecular docking simulations and dynamics simulations.Also,PC and TA showed the synergistic inhibition with orlistat.Fluorescence,UVvis and the thermodynamic analysis revealed that the complexes were formed from CEase and inhibitors by noncovalent interaction.As revealed by the circular dichroism results,both PC and TA decreased enzymatic activities by altering the conformations of CEase.The inhibition of PC and TA on CEase might be one mechanism for its cholesterol-lowering effect.

Associations between remnant cholesterol levels and mortality in patients with diabetes

BACKGROUND Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant cholesterol with all-cause and cardiovas-cular mortality in patients with diabetes.METHODS This prospective cohort study included 4740 patients with diabetes who par-ticipated in the National Health and Nutrition Examination Survey from 1999 through 2018.Remnant cholesterol was used as the exposure variable,and all-cause and cardiovascular mortality were considered outcome events.Outcome data were obtained from the National Death Index,and all participants were followed from the interview date until death or December 31,2019.Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes,in which remnant cholesterol was modeled as both a categorical and a continuous variable.Restricted cubic splines(RCSs)were calculated to assess the nonlinearity of associations.Subgroup(stratified by sex,age,body mass index,and duration of diabetes)and a series of sensitivity analyses were performed to evaluate the robustness of the associations.RESULTS During a median follow-up duration of 83 months,1370 all-cause deaths and 389 cardiovascular deaths were documented.Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality[hazard ratio(HR)95%confidence interval(CI):0.66(0.52-0.85)];however,when remnant cholesterol was modeled as a continuous variable,it was associated with increased risks of all-cause[HR(95%CI):1.12(1.02-1.21)per SD]and cardiovascular[HR(95%CI):1.16(1.01-1.32),per SD]mortality.The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality.Subgroup and sensitivity analyses did not reveal significant differences from the above results.CONCLUSION In patients with diabetes,higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality,and diabetes patients with slightly higher remnant cholesterol(0.68-1.04 mmol/L)had a lower risk of all-cause mortality.

Non-HDL-C水平和ApoB/ApoA1比值与初发心肌梗死的相关性研究

目的探究不同非高密度脂蛋白胆固醇(non-HDL-C)水平初次急性心肌梗死患者的临床特征及载脂蛋白B(Apo B)和载脂蛋白A1(Apo A1)比值以及non-HDL-C与冠状动脉(冠脉)病变程度的相关性。方法选取2021年12月至2023年4月于重庆医科大学附属第一医院心内科入院治疗的首次诊断为急性心肌梗死且行冠脉造影的患者410例。计算Apo B/Apo A1比值及non-HDL-C,根据non-HDL-C三分位数分为低non-HDL-C组(≤2.89 mmol/L)、中non-HDL-C组(2.9~4.16 mmol/L)、高non-HDL-C组(≥4.17 mmol/L),比较三组患者一般临床资料及冠脉病变特点的差异性。另采用Spearman秩相关和二元Logistics回归分析non-HDL-C水平、Apo B/Apo A1对冠脉病变严重程度的影响。结果与低non-HDL-C组相比,中non-HDL-C组和高non-HDL-C组患者年龄更小(P<0.05);高non-HDL-C组较另外两组具有更高水平的体质指数(BMI)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、ApoB、ApoA1、ApoB/ApoA1、白蛋白、γ-谷酰转移酶、尿酸(P<0.05)。三组间左前降支病变、回旋支病变、多支血管病变、Gensini评分相比,差异有统计学意义(P<0.05)。偏相关分析显示Apo B/Apo A1和non-HDL-C均与多支血管病变、Gensini评分呈正相关(P<0.05);多因素二元Logistics回归分析显示ApoB/ApoA1比值(OR=3.149,95%CI:1.209~8.201,P=0.019)、non-HDL-C≥4.17 mmol/L(OR=4.199,95%CI:1.524~11.565,P=0.006)是多支血管病变的独立危险因素。结论在初次急性心肌梗死青年患者有冠脉病变或(冠状动脉粥样硬化性心脏病)危险因素中,更应关注ApoB/ApoA1及non-HDL-C,同时严格控制non-HDL-C是心肌梗死患者潜在的降脂目标。

Causal associations between intermediate very-low-density lipoprotein cholesterol-to-total lipids ratio and peptic ulcer:A bidirectional Mendelian randomization study

BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of peptic ulcers(PU).However,the precise causal relationship between these factors remains ambiguous.Consequently,this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer.AIM To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein(VLDL)association with PU via genetic methods,guiding future clinical research.METHODS Genome-wide association study(GWAS)datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project(https://gwas.mrcieu.ac.uk).For the forward Mendelian randomization(MR)analysis,72 single nucleotide polymorphisms(SNPs)were identified as instrumental variables.These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL,with peptic ulcer as the outcome variable.Conversely,for the inverse MR analysis,no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome.All MR analyses utilized inverse variance weighted(IVW)as the primary analytical method.Additionally,weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects.Egger regression was used as a supplementary method to evaluate potential directional pleiotropy.Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing.RESULTS The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer(IVW:OR=2.557,95%CI=1.274-5.132,P=0.008).However,no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis.CONCLUSION In conclusion,our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers.However,further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

血清LDL-C/HDL-C、non-HDL-C、RLP-C及sLOX-1水平与老年急性脑梗死的相关性研究

目的分析血清低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)、非高密度脂蛋白胆固醇(non-HDL-C)、残粒脂蛋白胆固醇(RLP-C)及可溶性凝集素样氧化型低密度脂蛋白受体-1(sLOX-1)水平与老年急性脑梗死(ACI)的相关性。方法选取2022年1月—2023年8月收治的230例老年ACI作为研究组,另选择同期、同年龄段115例健康体检者作为对照组。比较2组LDL-C/HDL-C、non-HDL-C、RLP-C及sLOX-1水平,比较研究组不同斑块稳定性、神经功能缺损程度[采用美国国立卫生研究院卒中量表(NIHSS)评分评估]、颈动脉内中膜厚度(IMT)患者上述指标水平,偏回归分析上述指标与老年ACI的关系,并分析上述指标与斑块稳定性、IMT、NIHSS评分的相关性。结果研究组LDL-C/HDL-C、non-HDL-C、RLP-C、sLOX-1水平高于对照组(P<0.01)。老年ACI患者LDL-C/HDL-C、non-HDL-C、RLP-C及sLOX-1水平,无斑块患者<稳定斑块患者<不稳定斑块患者,轻度神经功能缺损患者<中度神经功能缺损患者<重度神经功能缺损患者,IMT正常患者<IMT增厚患者<斑块形成患者(P<0.05)。LDL-C/HDL-C、non-HDL-C、RLP-C、sLOX-1水平与老年ACI密切相关(P<0.01)。研究组LDL-C/HDL-C、non-HDL-C、RLP-C及sLOX-1水平分别与斑块稳定性、IMT、NIHSS评分呈正相关(P<0.01)。结论老年ACI患者LDL-C/HDL-C、non-HDL-C、RLP-C、sLOX-1水平明显升高,且与神经功能缺损程度及颈动脉粥样硬化斑块密切相关。

Non-HDL-C/HDL-C和NHR与冠状动脉病变严重程度的相关性

目的探讨非高密度脂蛋白胆固醇/高密度脂蛋白胆固醇比值(non-high-density lipoprotein cholesterol to high density lipoprotein cholesterol ratio,non-HDL-C/HDL-C)和中性粒细胞计数/高密度脂蛋白胆固醇比值(neutrophil to high-density lipoprotein cholesterol ratio,NHR)与冠状动脉病变严重程度的相关性。方法选取2022年1月至2023年6月因胸闷、胸痛于华北理工大学附属医院心内科住院初次行冠状动脉造影检查的患者284例,根据冠状动脉造影结果分为冠状动脉病变组(n=223)和对照组(n=61)。收集两组临床资料(一般资料和实验室资料),计算non-HDL-C/HDL-C和NHR,比较两组临床资料。根据Gensini评分将冠状动脉病变组分为低、高分值两个亚组,Gensini评分<30分为低分值亚组、Gensini评分≥30分为高分值亚组,比较两亚组实验室资料。采用Spearman相关性分析探讨冠状动脉病变患者Gensini评分与non-HDL-C/HDL-C、NHR的相关性。应用多因素Logistic回归分析探讨冠状动脉病变患者高Gensini评分的影响因素,并绘制受试者工作特征(receiver operating characteristic,ROC)曲线以评价non-HDL-C/HDL-C和NHR对冠状动脉病变患者高Gensini评分的预测价值。结果冠状动脉病变组non-HDL-C/HDL-C和NHR水平高于对照组(均P<0.05);Gensini评分高分值亚组non-HDL-C/HDL-C、NHR水平高于低分值亚组(均P<0.05)。相关性分析显示,non-HDL-C/HDL-C、NHR与Gensini评分均呈正相关(均P<0.05)。多因素Logistic回归分析显示,NHR升高是冠状动脉病变患者高Gensini评分的独立危险因素(OR=1.650,95%CI:1.262-2.158,P<0.05)。绘制ROC曲线,non-HDL-C/HDL-C和NHR预测冠状动脉病变严重程度的ROC曲线下面积分别为0.657(95%CI:0.582-0.732,P<0.01)和0.736(95%CI:0.666-0.807,P<0.01)。结论non-HDL-C/HDL-C、NHR与冠状动脉病变严重程度呈正相关,且NHR是冠状动脉病变患者高Gensini评分的独立预测因子。

肥胖儿童non-HDL-C、remnant cholesterol与亚临床动脉粥样硬化的关系

目的:了解non-HDL-C和remnant cholesterol与肥胖儿童亚临床动脉粥样硬化(AS)的关系。方法:根据甘油三酯(TG)水平将65例肥胖儿童(肥胖组)分为I组(TG≥2.3 mmol/L)32例,II组(TG<2.3 mmol/L)33例,与肥胖组儿童性别年龄相匹配的正常体质量儿童30例为III组(对照组)。比较3组儿童血脂指标,对肥胖组各项血脂指标与血浆致动脉粥样硬化指数(AIP)进行相关性分析,肥胖患儿体质指数、血脂指标与颈动脉内径、内膜-中层厚度(c-IMT)、血流参数进行相关性分析。结果:I组、II组的TG、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、non-HDL-C、remnant cholesterol、AIP均较对照组升高,高密度脂蛋白胆固醇(HDL-C)较对照组降低,且I组的remnant cholesterol、AIP均较II组升高。肥胖组儿童AIP与TG、non-HDL-C、remnant cholesterol呈正相关,与HDL-C呈负相关。37例行颈动脉超声检查的肥胖儿童的c-IMT较正常儿童的增厚。结论:non-HDL-C、remnant cholesterol在肥胖儿童亚临床AS中有重要作用,在肥胖儿童血脂异常的治疗中应关注non-HDL-C、remnant cholesterol的变化。

Chronic Supplementation with L-Isoleucine Alone or in Combination with Exercise Reduces Hepatic Cholesterol Levels with No Effect on Serum Glucose, Insulin, or Lipids in Rats Fed a High Fructose Diet

The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance and liver disease. Previous studies have cited improvements in glucose metabolism with a single dose of L-isoleucine (ILE). However, it is still unclear whether chronic consumption of ILE has any direct benefit. The objective of this study was to examine the influence of chronic ILE supplementation alone or in combination with exercise on fasting serum glucose, insulin, lipids, and lipoprotein cholesterol levels;glucose tolerance;and hepatic lipids in rats. Male Sprague-Dawley rats (n = 40) were divided into Control (low fructose diet);High Fructose diet (HF);HF plus 1.5% ILE (HF + ILE);HF plus exercise (HF + EX);and HF plus 1.5% ILE and exercise (HF + ILE + EX). The HF diets consisted of 70% kcalories from fructose. After 6 weeks of treatment, no significant differences were observed between groups for changes in fasting serum glucose, insulin, lipids, or lipoprotein cholesterol levels. However, hepatic total cholesterol was significantly lower in the HF + ILE + EX compared to the Control and HF, while, the HF + ILE had significantly lower hepatic free cholesterol compared to the HF. We also found no differences between groups for serum glucose response following an oral glucose tolerance test. In conclusion, our study shows that ILE supplementation in rats does not influence serum glucose and lipid biomarkers but may have an influence on lipid metabolic pathways within the liver.

Thrombin increases the expression of cholesterol 25-hydroxylase in rat astrocytes after spinal cord injury

Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols,which have profound effects on neuropathology.25-Hydroxycholesterol(25-HC),the main product of the membrane-associated enzyme cholesterol-25-hydroxylase(CH25H),plays important roles in mediating neuroinflammation.However,whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC,as well as the resulting pathological effects,remain unclear.In the present study,spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression.A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo.In cultured primary astrocytes,thrombin interacted with protease-activated receptor 1,mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway.Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration.Finally,injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function.Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention

Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.

The role of cholesterol in modifying the lipid-lowering effects of Fuzhuan brick-tea in Caenorhabditis elegans via SBP-1/SREBP

Fuzhuan brick-tea(FZT)has long been consumed for its supposed weight loss and lipid-lowering benefi ts.In this study,we show that the regulation of fat storage in Caenorhabditis elegans from a water extract of FZT was affected by cholesterol levels.We found that FZT signifi cantly decreased fat storage under normal cholesterol levels or in a cholesterol-free diet,while lipid accumulation was increased for a high cholesterol diet.Moreover,this mechanism may involve the conserved sterol regulatory element-binding protein(SREBP)/mediator-15(MDT-15)signaling pathway and the nuclear hormone receptor NHR-80.In addition,lipid synthesis-related genes inhibited by FZT were partially affected by a cholesterol-free diet.Thus,our fi ndings suggested that the potential lipid-lowering effects of FZT may depend on the cholesterol level,which may help to improve the consumption of FZT.

Mechanism of Niacin Induced Hot Flushes and Suppression of Cholesterol

Niacin or nicotinic acid is a form of B3 vitamin prescribed at higher concentrations for the suppression of cholesterol levels. Supplemental doses may cause very little or no side effects. However, higher concentrations of niacin cause hot flushes for most people. Here we propose a biochemical mechanism of niacin induced hot flushes. Orally taken prescription doses of niacin are converted to NAD with the liberation of excess pyrophosphate which in turn releases energy in the form of heat (hot flushes through capsaicin receptor) by the action of pyrophosphatases. The excess pyrophosphate may suppress cholesterol biosynthesis through feedback mechanism. The pathways of NAD and cholesterol biosynthesis were discussed with refence to the production and function of pyrophosphate.

Cytotoxicity of Cholesterol Oxides and the Consequences of Relative Molecular Similarity to cGMP Nucleotide

Cholesterol and cholesterol oxides impact on the functional properties of cells, in respect of the intracellular and extracellular distribution of compounds across cell membranes, carcinogenesis and drug resistance. Abnormal levels of cholesterol oxides and steroids in cancerous tissues promote interest in steroid receptor cross-talk during cell-signalling and the steroid metabolome of cancer patients. The research literature links the cytotoxic properties of oxysterols to interference with the NO/cGMP pathway. cGMP participates in cell-signalling and has a molecular structure that relates to cancer-inducing and cancer-preventing agents. This study uses a molecular modelling approach to compare the structures of cholesterol oxides to cGMP. Cholesterol and cholesterol oxide structures fit to a cGMP structural template in several ways, some of which are replicated by corticosteroids and gonadal steroid hormones. The results of this study support the concept that cholesterol oxides modulate cell apoptosis and autophagy via the NO/cGMP pathway and in conjunction with steroid hormones participate in modulating regulation of cell function by cGMP.

Cholesterol paradox in the community-living old adults:is higher better?

OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 com-munity older adults.After the baseline survey,the last follow-up was March 31,2021 with an average 8.13 years of follow-up.Cox proportional hazard model was used to estimate the hazard ratios(HR)with 95%CI for cardiovascular disease(CVD)death and all-cause death in associations with baseline lipid indicators.RESULTS A total of 4499 participants were recruited,and the mean levels of uric acid,body mass index,systolic blood pres-sure,diastolic blood pressure,fasting plasma glucose,total cholesterol(TC),triglyceride,and low-density lipoprotein cholesterol(LDL-C)showed an upward trend with the increasing remnant cholesterol(RC)quarters(Ptrend<0.05),while the downward tr-end was found in high-density lipoprotein cholesterol(HDL-C).During the total 36,596 person-years follow-up,the CVD mortal-ity and all-cause mortality during an average 8.13 years of follow-up was 3.87%(95%CI:3.30%-4.43%)and 14.83%(95%CI:13.79%-15.86%)with 174 CVD death participants and 667 all-cause death participants.After adjusting for confounders,the higher level of TC(HR=0.854,95%CI:0.730-0.997),LDL-C(HR=0.817,95%CI:0.680-0.982)and HDL-C(HR=0.443,95%CI:0.271-0.724)were associated with lower risk of CVD death,and the higher level of HDL-C(HR=0.637,95%CI:0.501-0.810)were associated with lower risk of all-cause death.The higher level of RC(HR=1.276,95%CI:1.010-1.613)increase the risk of CVD death.Com-pared with the normal lipid group,TC≥6.20 mmol/L group and LDL-C≥4.10 mmol/L group were no longer associated with lower risk of CVD death,while RC≥0.80 mmol/L group was still associated with higher risk of CVD death.In normal lipid gr-oup,the higher levels of TC,LDL-C and HDL-C were related with lower CVD death.CONCLUSIONS In community older adults,higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range.Higher RC was associated with higher CVD mortality,which may be a better lipid indicator for es-timating the CVD death risk in older adults.