AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieve...AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.展开更多
In our examination of the distribution of abdominal fat,dietary intake and biochemical data in patients with nonalcoholic fatty liver disease(NAFLD),non-obese NAFLD patients without insulin resistance presented a char...In our examination of the distribution of abdominal fat,dietary intake and biochemical data in patients with nonalcoholic fatty liver disease(NAFLD),non-obese NAFLD patients without insulin resistance presented a characteristic pattern of dietary intake.Dietary cholesterol intake was superabundant in non-obese patients compared with obese patients,although total energy and carbohydrate intake was not excessive.Namely,excess cholesterol intake appears to be one of the main factors associated with NAFLD development and liver injury.Therefore,the control of dietary cholesterol intake may lead to an improvement in NAFLD,and the NPC1L1 inhibitor ezetimibe might be a promising treatment for NAFLD.We review one pathogenic aspect of lipid metabolism dysregulation in NAFLD and survey new strategies for NAFLD treatment based on the modification of cholesterol metabolism.展开更多
Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary man...Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil(cholesterol free diet) and 1% HC containing 12% olive oil(HC+OO) enriched with MUFA and 12% sunflower oil(HC+SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results: Comparatively, rats treated with HC+OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC+SO diet(P<0.05). Otherwise, HC+OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions: HC+OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC+SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC+OO diet can be caused by the delay in the FA release to the blood.展开更多
Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of un...Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.展开更多
Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the pre- cursor for steroid hormones and vitamin D. How...Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the pre- cursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily thought to be responsible for the disposal of cholesterol is called reverse cholesterol transport (RCT). Therefore, RCT is seen as an interesting target for the development of drugs aimed at the prevention of atherosclerosis. Research on RCT has taken off in recent years. In this review, the classical concepts about RCT are discussed, together with new insights about this topic.展开更多
Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of S...Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.展开更多
Introduction: This study was conducted in the University of Port Harcourt Teaching Hospital, with the sample analysis conducted in HMG Hospital private laboratory in Rivers State. Methodology: A random sampling techni...Introduction: This study was conducted in the University of Port Harcourt Teaching Hospital, with the sample analysis conducted in HMG Hospital private laboratory in Rivers State. Methodology: A random sampling technique was employed to select the respondents, while the Taro-Yamene formula was used to calculate the sample size and data analysed with SPSS version 20. Results: The respondents were mainly aged 30 - 39 years, 12 (40.00%), mainly females, 20 (66.67%) and obese, 16 (53.33%). They were also mainly Christians, 25 (83.33%), of Ijaw descent 20 (66.67%) and civil/public servants, 13 (43.33%). The total cholesterol was the highest, 18 (60.00%), normal for triglyceride, 24 (80.00%), low for high density lipoprotein cholesterol, 22 (73.33%) and high for low density lipoprotein cholesterol, 14 (46.67%). Maximum liver span was statistically significant to triglyceride concentration;p-value (0.001) but not for total cholesterol;p-value (0.084), high density lipoprotein cholesterol;p-value (0.477) and low density lipoprotein cholesterol;p-value (0.317). Conclusion: Liver span is a predictive tool for the probable diagnosis of dyslipidaemia.展开更多
Objective:To investigate the relationship between malaria parasite status and cholesterol level of 110 consenting subjects(55 patients and 55 controls) in parts of the Imo River Basin of Nigeria. Methods:Giemsa staini...Objective:To investigate the relationship between malaria parasite status and cholesterol level of 110 consenting subjects(55 patients and 55 controls) in parts of the Imo River Basin of Nigeria. Methods:Giemsa staining was used for malaria parasite examination while Randox cholesterol kit was used for cholesterol level estimation.Results:About 49 persons(90%) with malaria had low cholesterol(【180 mg/dL).Highest mean cholesterol levels were 274 mg/dL for study patients and 220 mg/dL for controls respectively;Lowest mean cholesterol levels were 168 mg/dL (patienls) and 138 mg/dL(controls) respectively.Low cholesterol levels(【 180 mg/dL) were found in patients(84%) and controls(6%) respectively.However.16.4%of controls and 6%of patients had borderline cholesterol level(200-239 mg/dL).This study establishes a significant correlation(12.9%.P【0.01) between malaria parasite status and cholesterol level.Conclusions: These findings imply that choleslerol level estimation may be a potential concurrent and valuable diagnosis for malaria status.展开更多
Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Sinc...Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.展开更多
Aim: To investigate the roles of liver X receptors (LXR) in the lipid composition and gene expression regulation in the murine caput epididymidis. LXR are nuclear receptors for oxysterols, molecules derived from ch...Aim: To investigate the roles of liver X receptors (LXR) in the lipid composition and gene expression regulation in the murine caput epididymidis. LXR are nuclear receptors for oxysterols, molecules derived from cholesterol metabolism that are present in mammals as two isoforms: LXRα, which is more specifically expressed in lipid-metabolising tissues, such as liver, adipose and steroidogenic tissues, and macrophages, whereas LXRβ is ubiquitous. Their importance in reproductive physiology has been sustained by the fact that male mice in which the function of both LXR has been disrupted have fertility disturbances starting at the age of 5 months, leading to complete sterility by the age of 9 months. These defects are associated with epididymal epithelial degeneration in caput segments one and two, and with a sperm midpiece fragility, leading to the presence of isolated sperm heads and flagella when luminal contents are recovered from the cauda epididymidis. Methods: The lipid composition of the caput epididymidis of wild-type and LXR-deficient mice was assessed using oil red O staining on tissue cryosections and lipid extraction followed by high performance liquid chromatography or gas chromatography. Gene expression was checked by quantitative real time polymerase chain reaction. Results: Using LXR-deficient mice, we showed an alteration of the lipid composition of the caput epididymidis as well as a significantly decreased expression of the genes encoding SREBPlc, SCD1 and SCD2, involved in fatty acid metabolism. Conclusion: Altogether, these results show that LXR are important regulators of epididymal function, and play a critical role in the lipid maturation processes occurring during sperm epididymal maturation. (Asian J Androl 2007 July; 9: 574-582)展开更多
AIM To assess the association between liver fat content(LFC) and weight status in young adults using proton magnetic resonance spectroscopy(1H MRS) technique.METHODSSeventy-eight healthy young adults, between 19-30 ye...AIM To assess the association between liver fat content(LFC) and weight status in young adults using proton magnetic resonance spectroscopy(1H MRS) technique.METHODSSeventy-eight healthy young adults, between 19-30 years of age participated in this study. This group was then separated into a control of 39 subjects and an overweight/obese group(OW/OB group) consisting of 39 subjects. Blood biochemical quantity and 1 H MRS was performed for LFC assessment.RESULTS LFC was found to be almost three times higher in OW/OB group when compared to the control group. A 48.7% incidence of non-alcoholic fatty liver disease in the OW/OB group was found. Blood biochemical measurements showed statistically higher low-density lipoproteins and triglyceride, lower highdensity lipoproteins, and increased glycosylated hemoglobin and fasting glucose in the OW/OB group. Body mass index was a significant independent predictor for LFC after adjusting for age and sex(multiple linear regression; β = 0.459, P <0.001).CONCLUSION Due to the prevalence of high LFC in the OW/OB group, it can be proposed that weight gain and obesity are sensitive indicators of high hepatic fat content.展开更多
ABSTRACT:Two separate studies tested the hypoth- esis that plasma low-density lipoprotein cholesterol LDL-C ) can be decreased by conjugated linoleic acid (CLA) by depressing hepatic acyl-coenzyme A: cholesterol...ABSTRACT:Two separate studies tested the hypoth- esis that plasma low-density lipoprotein cholesterol LDL-C ) can be decreased by conjugated linoleic acid (CLA) by depressing hepatic acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity. In the first experiment, 3 groups of 6 early-weaned piglets were fed low-fat diets containing either 1.5% CLA, 1.5% corn oil or 1.5% beef tallow;fat provided 8% of the energy intake. In the second experiment, 4 groups of 6 early-weaned piglets were fed high-fat di- ets containing either 15% beef tallow, 12% beef tal- low plus 3% CLA, 15% corn oil, or 12% corn oil plus 3% CLA; fat provided 29% of energy intake. Cholesterol was balanced across diets in both experi-ments. In pigs fed the low-fat diets, all dietary fats in- creased LDL-C and triacylglycerols and decreased high-density lipoprotein cholesterol ( HDL-C ) and very low-density lipoprotein cholesterol (VLDL-C). LDL-C was the same in pigs fed low-fat tallow or low-fat CLA diets. However, ACAT activity was near- ly 80% higher in pigs fed the low-fat tallow diet than in pigs fed the low-fat CLA diets. All high-fat diets increased LDL-C, HDL-C and triacylglycerols equally with no effect on VLDL-C. There were no unique fat- ty acid effects of the high-fat diets on ACAT activity. We conclude that supplemental fats had differential effects on hepatic ACAT activity and LDL-C, but on- ly in pigs fed low-fat diets.展开更多
Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic disea...Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage disease.Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency.By contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene.In the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease.Patients with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis.Among cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL activity.These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD.Moreover,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.展开更多
AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory...AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.展开更多
目的探究甘油三酯与高密度脂蛋白胆固醇比值(TG/HDL-C)对原发性肝癌发病的影响。方法采用前瞻性队列研究的方式,收集2006年7月—2007年12月参加开滦集团健康体检的99750例在职及离退休职工的体检资料,并对其原发性肝癌的发病情况进行随...目的探究甘油三酯与高密度脂蛋白胆固醇比值(TG/HDL-C)对原发性肝癌发病的影响。方法采用前瞻性队列研究的方式,收集2006年7月—2007年12月参加开滦集团健康体检的99750例在职及离退休职工的体检资料,并对其原发性肝癌的发病情况进行随访,随访截止时间为2021年12月31日。根据TG/HDL-C三分位水平将受试者分成3组,分别为Q1组(TC/HDL-C<0.66,n=33229)、Q2组(0.66≤TC/HDL-C<1.14,n=33302)、Q3组(TC/HDL-C≥1.14,n=33219)。计算各组原发性肝癌的发病密度。符合正态分布的计量资料多组间比较采用单因素方差分析;符合偏态分布的计量资料多组间比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。采用Kaplan⁃Meier法计算各组原发性肝癌的累积发病率,以Logrank检验比较各组间累积发病率的差异。采用Cox比例风险模型分析不同TG/HDL-C水平分组对原发性肝癌发病的影响。结果3组受试者年龄、男性比例、腰围、BMI、空腹血糖、收缩压、舒张压、TG、TC、HDL-C、LDL-C、ALT、超敏C-反应蛋白、慢性肝病、高血压病、糖尿病、恶性肿瘤家族史、饮酒、吸烟、体育锻炼、受教育程度组间对比差异均有统计学意义(P值均<0.05)。在平均(14.06±2.71)年的随访过程中,新发肝癌共计484例,其中男446例,女38例。Q1组、Q2组、Q3组原发性肝癌的发病密度分别是0.39/千人年、0.35/千人年、0.30/千人年。3组受试者的原发性肝癌累积发病率分别是6.03‰、5.28‰和4.49‰,经Log-rank检验,差异有统计学意义(χ^(2)=6.06,P=0.048)。校正了考虑到的混杂因素后,Cox比例风险模型结果显示,以Q3组为对照,Q1、Q2组的风险比及95%可信区间分别为2.04(1.61~2.58)、1.53(1.21~1.92)(P for trend<0.05)。结论TG/HDL-C水平降低与原发性肝癌发病风险升高有关,特别是在慢性肝病的人群中这种关联更加明显。展开更多
基金Supported by The Medical Faculty of the Heinrich Heine University Düsseldorf
文摘AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.
文摘In our examination of the distribution of abdominal fat,dietary intake and biochemical data in patients with nonalcoholic fatty liver disease(NAFLD),non-obese NAFLD patients without insulin resistance presented a characteristic pattern of dietary intake.Dietary cholesterol intake was superabundant in non-obese patients compared with obese patients,although total energy and carbohydrate intake was not excessive.Namely,excess cholesterol intake appears to be one of the main factors associated with NAFLD development and liver injury.Therefore,the control of dietary cholesterol intake may lead to an improvement in NAFLD,and the NPC1L1 inhibitor ezetimibe might be a promising treatment for NAFLD.We review one pathogenic aspect of lipid metabolism dysregulation in NAFLD and survey new strategies for NAFLD treatment based on the modification of cholesterol metabolism.
文摘Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil(cholesterol free diet) and 1% HC containing 12% olive oil(HC+OO) enriched with MUFA and 12% sunflower oil(HC+SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results: Comparatively, rats treated with HC+OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC+SO diet(P<0.05). Otherwise, HC+OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions: HC+OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC+SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC+OO diet can be caused by the delay in the FA release to the blood.
文摘Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.
文摘Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the pre- cursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily thought to be responsible for the disposal of cholesterol is called reverse cholesterol transport (RCT). Therefore, RCT is seen as an interesting target for the development of drugs aimed at the prevention of atherosclerosis. Research on RCT has taken off in recent years. In this review, the classical concepts about RCT are discussed, together with new insights about this topic.
基金Supported by Top Institute Pharma (TIPharma Project T2-110 Hoekstra M and Van Berkel TJC)+2 种基金Grant 2008T070 from the Netherlands Heart Foundation (Hoekstra M)VIDI Grant 917.66.301 from the Netherlands Organization for Scientific Research (Van Eck M)Van Eck Mis an Established Investigator of the Netherlands Heart Foundation (Grant 2007T056)
文摘Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.
文摘Introduction: This study was conducted in the University of Port Harcourt Teaching Hospital, with the sample analysis conducted in HMG Hospital private laboratory in Rivers State. Methodology: A random sampling technique was employed to select the respondents, while the Taro-Yamene formula was used to calculate the sample size and data analysed with SPSS version 20. Results: The respondents were mainly aged 30 - 39 years, 12 (40.00%), mainly females, 20 (66.67%) and obese, 16 (53.33%). They were also mainly Christians, 25 (83.33%), of Ijaw descent 20 (66.67%) and civil/public servants, 13 (43.33%). The total cholesterol was the highest, 18 (60.00%), normal for triglyceride, 24 (80.00%), low for high density lipoprotein cholesterol, 22 (73.33%) and high for low density lipoprotein cholesterol, 14 (46.67%). Maximum liver span was statistically significant to triglyceride concentration;p-value (0.001) but not for total cholesterol;p-value (0.084), high density lipoprotein cholesterol;p-value (0.477) and low density lipoprotein cholesterol;p-value (0.317). Conclusion: Liver span is a predictive tool for the probable diagnosis of dyslipidaemia.
文摘Objective:To investigate the relationship between malaria parasite status and cholesterol level of 110 consenting subjects(55 patients and 55 controls) in parts of the Imo River Basin of Nigeria. Methods:Giemsa staining was used for malaria parasite examination while Randox cholesterol kit was used for cholesterol level estimation.Results:About 49 persons(90%) with malaria had low cholesterol(【180 mg/dL).Highest mean cholesterol levels were 274 mg/dL for study patients and 220 mg/dL for controls respectively;Lowest mean cholesterol levels were 168 mg/dL (patienls) and 138 mg/dL(controls) respectively.Low cholesterol levels(【 180 mg/dL) were found in patients(84%) and controls(6%) respectively.However.16.4%of controls and 6%of patients had borderline cholesterol level(200-239 mg/dL).This study establishes a significant correlation(12.9%.P【0.01) between malaria parasite status and cholesterol level.Conclusions: These findings imply that choleslerol level estimation may be a potential concurrent and valuable diagnosis for malaria status.
文摘Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.
文摘Aim: To investigate the roles of liver X receptors (LXR) in the lipid composition and gene expression regulation in the murine caput epididymidis. LXR are nuclear receptors for oxysterols, molecules derived from cholesterol metabolism that are present in mammals as two isoforms: LXRα, which is more specifically expressed in lipid-metabolising tissues, such as liver, adipose and steroidogenic tissues, and macrophages, whereas LXRβ is ubiquitous. Their importance in reproductive physiology has been sustained by the fact that male mice in which the function of both LXR has been disrupted have fertility disturbances starting at the age of 5 months, leading to complete sterility by the age of 9 months. These defects are associated with epididymal epithelial degeneration in caput segments one and two, and with a sperm midpiece fragility, leading to the presence of isolated sperm heads and flagella when luminal contents are recovered from the cauda epididymidis. Methods: The lipid composition of the caput epididymidis of wild-type and LXR-deficient mice was assessed using oil red O staining on tissue cryosections and lipid extraction followed by high performance liquid chromatography or gas chromatography. Gene expression was checked by quantitative real time polymerase chain reaction. Results: Using LXR-deficient mice, we showed an alteration of the lipid composition of the caput epididymidis as well as a significantly decreased expression of the genes encoding SREBPlc, SCD1 and SCD2, involved in fatty acid metabolism. Conclusion: Altogether, these results show that LXR are important regulators of epididymal function, and play a critical role in the lipid maturation processes occurring during sperm epididymal maturation. (Asian J Androl 2007 July; 9: 574-582)
基金Supported by Faculty of Associated Medical Sciences,Chiang Mai University,Chiang Mai,Thailand,No.6593(4)1180
文摘AIM To assess the association between liver fat content(LFC) and weight status in young adults using proton magnetic resonance spectroscopy(1H MRS) technique.METHODSSeventy-eight healthy young adults, between 19-30 years of age participated in this study. This group was then separated into a control of 39 subjects and an overweight/obese group(OW/OB group) consisting of 39 subjects. Blood biochemical quantity and 1 H MRS was performed for LFC assessment.RESULTS LFC was found to be almost three times higher in OW/OB group when compared to the control group. A 48.7% incidence of non-alcoholic fatty liver disease in the OW/OB group was found. Blood biochemical measurements showed statistically higher low-density lipoproteins and triglyceride, lower highdensity lipoproteins, and increased glycosylated hemoglobin and fasting glucose in the OW/OB group. Body mass index was a significant independent predictor for LFC after adjusting for age and sex(multiple linear regression; β = 0.459, P <0.001).CONCLUSION Due to the prevalence of high LFC in the OW/OB group, it can be proposed that weight gain and obesity are sensitive indicators of high hepatic fat content.
基金Supported by USDA/CSREES Competitive Grant 98-35206-6286federal funds from the USDA,ARS under Cooperative Agreement no.58-6250-1-003
文摘ABSTRACT:Two separate studies tested the hypoth- esis that plasma low-density lipoprotein cholesterol LDL-C ) can be decreased by conjugated linoleic acid (CLA) by depressing hepatic acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity. In the first experiment, 3 groups of 6 early-weaned piglets were fed low-fat diets containing either 1.5% CLA, 1.5% corn oil or 1.5% beef tallow;fat provided 8% of the energy intake. In the second experiment, 4 groups of 6 early-weaned piglets were fed high-fat di- ets containing either 15% beef tallow, 12% beef tal- low plus 3% CLA, 15% corn oil, or 12% corn oil plus 3% CLA; fat provided 29% of energy intake. Cholesterol was balanced across diets in both experi-ments. In pigs fed the low-fat diets, all dietary fats in- creased LDL-C and triacylglycerols and decreased high-density lipoprotein cholesterol ( HDL-C ) and very low-density lipoprotein cholesterol (VLDL-C). LDL-C was the same in pigs fed low-fat tallow or low-fat CLA diets. However, ACAT activity was near- ly 80% higher in pigs fed the low-fat tallow diet than in pigs fed the low-fat CLA diets. All high-fat diets increased LDL-C, HDL-C and triacylglycerols equally with no effect on VLDL-C. There were no unique fat- ty acid effects of the high-fat diets on ACAT activity. We conclude that supplemental fats had differential effects on hepatic ACAT activity and LDL-C, but on- ly in pigs fed low-fat diets.
文摘Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage disease.Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency.By contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene.In the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease.Patients with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis.Among cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL activity.These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD.Moreover,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.
文摘AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.
文摘目的探究甘油三酯与高密度脂蛋白胆固醇比值(TG/HDL-C)对原发性肝癌发病的影响。方法采用前瞻性队列研究的方式,收集2006年7月—2007年12月参加开滦集团健康体检的99750例在职及离退休职工的体检资料,并对其原发性肝癌的发病情况进行随访,随访截止时间为2021年12月31日。根据TG/HDL-C三分位水平将受试者分成3组,分别为Q1组(TC/HDL-C<0.66,n=33229)、Q2组(0.66≤TC/HDL-C<1.14,n=33302)、Q3组(TC/HDL-C≥1.14,n=33219)。计算各组原发性肝癌的发病密度。符合正态分布的计量资料多组间比较采用单因素方差分析;符合偏态分布的计量资料多组间比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。采用Kaplan⁃Meier法计算各组原发性肝癌的累积发病率,以Logrank检验比较各组间累积发病率的差异。采用Cox比例风险模型分析不同TG/HDL-C水平分组对原发性肝癌发病的影响。结果3组受试者年龄、男性比例、腰围、BMI、空腹血糖、收缩压、舒张压、TG、TC、HDL-C、LDL-C、ALT、超敏C-反应蛋白、慢性肝病、高血压病、糖尿病、恶性肿瘤家族史、饮酒、吸烟、体育锻炼、受教育程度组间对比差异均有统计学意义(P值均<0.05)。在平均(14.06±2.71)年的随访过程中,新发肝癌共计484例,其中男446例,女38例。Q1组、Q2组、Q3组原发性肝癌的发病密度分别是0.39/千人年、0.35/千人年、0.30/千人年。3组受试者的原发性肝癌累积发病率分别是6.03‰、5.28‰和4.49‰,经Log-rank检验,差异有统计学意义(χ^(2)=6.06,P=0.048)。校正了考虑到的混杂因素后,Cox比例风险模型结果显示,以Q3组为对照,Q1、Q2组的风险比及95%可信区间分别为2.04(1.61~2.58)、1.53(1.21~1.92)(P for trend<0.05)。结论TG/HDL-C水平降低与原发性肝癌发病风险升高有关,特别是在慢性肝病的人群中这种关联更加明显。