Excess Iodine and High-Fat Diet Combination Modulates Lipid Profile, Thyroid Hormone, and Hepatic LDLr Expression Values in Mice

The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200 μg/L iodine for 1, 3, or 6 months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6 months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (p < 0.05). LDLr expression in liver was increased significantly (p < 0.05) and parallel to the change of serum TC and TG. TT3 and TT4 levels in serum were elevated and TSH decreased significantly (p < 0.05). Liver type I iodothyronine deiodinase activity was significantly higher (p < 0.05) than control at the end of 6 months. Moreover, a time course damage effect of excess iodine combined with high-fat diet on thyroid glands was observed. The present findings demonstrated that excess iodine combined with high-fat diet could cause damage to thyroid glands and lead to thyroid hormone disorder. Those in turn caused the upregulation of hepatic LDLr gene, which resulted in the disorder in serum lipids.     

新疆贫困地区维吾尔族农民肥胖与血脂异常相关性研究

肥胖及血脂异常研究很少涉及低收入地区。本研究分析了新疆低收入地区维吾尔族农民体质指数(BMI)、超重及肥胖与多种血脂分子异常的关系,探讨贫困地区筛查高危人群的适宜策略。在新疆喀什农村对3 286名年龄≥18岁个体(男1 585人,女1 701人) 进行问卷检查、体格检查及多项血脂分子的检测。数据采用Pearson相关性、ROC、Logistic回归等统计学分析。结果显示,在男女性中,随着BMI的增加,甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)的血浓度呈现递增趋势（P<0.01）;男/女性TG、LDLC、TC血浓度均与BMI有显著相关性(P<0.01)。单项或多项血脂异常率均随BMI增加而上升;同一个体2个血脂指标同时异常的高危组合分别是TG+HDLC(高密度脂蛋白胆固醇)和TC+TG。Logistic联合多变量ROC曲线分析表明, 单项指标HDLC(AUC=089)在血脂异常诊断中的权重最高;而组合指标TG+HDLC(AUC=095)的权重高于其它任何组合。单因素Logistic回归分析发现,超重和肥胖是代谢综合征相关血脂指标TG、TC和HDLC异常的危险因素(P<0.05)。上述结果表明,在南疆农村贫困维吾尔族人群中,男女性超重与肥胖者均与血脂指标异常升高相关;HDLC、TG和 TC 任意两个指标同时异常,为血脂异常的高危状态。肥胖伴有“TG+HDLC”异常升高可能是血脂异常相关疾病的“集合危险因素”,在贫困地区具有临床筛查参考价值。     

番茄皂苷A对小鼠血脂及肝脏脂肪的作用

该研究以ApoE基因缺陷小鼠和高脂饲料诱导的高血脂症模型小鼠为对象,采用药理学方法研究了番茄皂苷A对血脂及肝脏脂肪的调节作用。在ApoE基因缺陷小鼠和高脂饲料诱导的高血脂症模型小鼠中,通过灌胃给予番茄皂苷A:取血,测定血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素氮(BUN)、肌酐(Cr)、葡萄糖(Glu)的含量和活性;处死小鼠后,取肝脏称重,计算肝脏指数;精确称取一部分肝脏,测定肝脏脂质的含量。结果表明:番茄皂苷A对ApoE基因缺陷小鼠可以降低血清TC、HDLC、LDLC的含量,对ALT、AST、BUN、Cr、Glu没有影响,说明番茄皂苷A可以降低ApoE基因缺陷小鼠血中胆固醇含量,对血糖没有影响,对肝肾功能无影响;对高脂饲料诱导的高血脂症模型小鼠,可以降低血清TC、HDLC的含量,可以降低肝脏TC的含量,对ALT、AST、BUN、Cr、Glu没有影响,说明番茄皂苷A可以改善高脂饲料诱导的高血脂症模型小鼠的脂质代谢,且对肝肾功能无影响。该研究结果表明番茄皂苷A具有一定的降低胆固醇的作用,且不影响肝肾功能。     

THE INFLUENCE OF THYROID FUNCTION AND BONE TURNOVER ON LIPOPROTEIN PROFILE IN YOUNG PHYSICALLY ACTIVE MEN WITH DIFFERENT INSULIN SENSITIVITY

Physical activity induces changes in the endocrine system. Previous data indicated that changes in insulin secretion and the tissue response to this hormone are very important for energy metabolism. It is believed that they are accompanied by changes in lipid metabolism, but factors contributing to this process are still disputed. The aim of this study was to assess interactions among insulin sensitivity, thyroid function, a bone turnover marker and serum lipid profile in young physically active men. Eighty-seven physical education students, aged 18-23 years, participated in the study. We measured serum levels of glucose, lipids, insulin, thyroid-stimulating hormone (TSH), osteocalcin and anthropometric parameters. Insulin sensitivity was determined using homeostatic model assessment for insulin resistance (HOMA-IR). The median value of HOMA-IR (1.344) was used to divide the study population into Group A (above the median) and Group B (below the median). Men from both groups did not differ in anthropometric parameters or in daily physical activity. Triglycerides (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were higher in Group A (P < 0.05). TSH and osteocalcin levels were similar in males with different HOMA-IR. Multiple regression analysis for TSH and osteocalcin showed that in Group A these hormones had no effect on plasma lipoproteins. However, in Group B they significantly determined the variation of plasma TC and low-density lipoprotein cholesterol (LDL-C) levels (in about 28% and 29%, respectively). We concluded that TSH and osteocalcin are involved in determination of a more healthy lipid profile at a certain level of insulin sensitivity.     

新疆贫困地区维吾尔族农民肥胖与血脂异常相关性研究

肥胖及血脂异常研究很少涉及低收入地区。本研究分析了新疆低收入地区维吾尔族农民体质指数(BMI)、超重及肥胖与多种血脂分子异常的关系,探讨贫困地区筛查高危人群的适宜策略。在新疆喀什农村对3 286名年龄≥18岁个体(男1 585人,女1 701人) 进行问卷检查、体格检查及多项血脂分子的检测。数据采用Pearson相关性、ROC、Logistic回归等统计学分析。结果显示,在男女性中,随着BMI的增加,甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)的血浓度呈现递增趋势（P<0.01）;男/女性TG、LDLC、TC血浓度均与BMI有显著相关性(P<0.01)。单项或多项血脂异常率均随BMI增加而上升;同一个体2个血脂指标同时异常的高危组合分别是TG+HDLC(高密度脂蛋白胆固醇)和TC+TG。Logistic联合多变量ROC曲线分析表明, 单项指标HDLC(AUC=089)在血脂异常诊断中的权重最高;而组合指标TG+HDLC(AUC=095)的权重高于其它任何组合。单因素Logistic回归分析发现,超重和肥胖是代谢综合征相关血脂指标TG、TC和HDLC异常的危险因素(P<0.05)。上述结果表明,在南疆农村贫困维吾尔族人群中,男女性超重与肥胖者均与血脂指标异常升高相关;HDLC、TG和 TC 任意两个指标同时异常,为血脂异常的高危状态。肥胖伴有“TG+HDLC”异常升高可能是血脂异常相关疾病的“集合危险因素”,在贫困地区具有临床筛查参考价值。     

Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor.

Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin resistance, and diabetes, all of which are components of a multiple risk factor syndrome that, along with hypercholesterolemia, precipitates a potential high risk for atherosclerosis. In the current study, we show an unexpectedly severe hyperlipidemia in ob/ob mice on a background of low density lipoprotein receptor (LDLR) deficiency (-/-). Doubly mutant mice (LDLR-/-;ob/ob) exhibited striking elevations in both total plasma cholesterol (TC) and triglyceride (TG) levels (1715 +/- 87 and 1016 +/- 172 mg/dl, respectively), at age 3-4 months, resulting in extensive atherosclerotic lesions throughout the aorta by 6 months. Lipoprotein analyses revealed the elevated TC and TG levels to be due to a large increase in an apoB-containing broad-beta remnant lipoprotein fraction. While fasting, diet restriction, and low level leptin treatment significantly lowered TG levels, they caused only slight changes in TC levels. Hepatic cholesterol and triglyceride contents as well as mRNA levels of cholesterologenic and lipogenic enzymes suggest that leptin deficiency increased hepatic triglyceride production but did not change cholesterol production in ob/ob mice regardless of their LDLR genotype. These data provide evidence that the hypertriglyceridemia and hypercholesterolemia in the doubly mutant mice are caused by distinct mechanisms and point to the possibility that leptin might have some impact on plasma cholesterol metabolism, possibly through an LDLR-independent pathway. This model will be an excellent tool for future studies on the relationship between impaired fuel metabolism, increased plasma remnant lipoproteins, diabetes, and atherosclerosis.     

成人原发肾病综合征病理类型与血脂代谢紊乱的关系

目的：研究成人原发肾病综合征(PNS)肾脏病理改变与血脂代谢紊乱的关系。方法：选取成人PNS患者109 例为研究对象, 分析不同病理类型PNS 患者血脂及血清脂蛋白代谢异常的发生率、代谢水平及胆固醇代谢异常的相关因素。结果：成人PNS 患 者血清总胆固醇(TC)升高、低密度脂蛋白胆固醇(LDL-C)升高、高密度脂蛋白胆固醇(HDL-C)降低、甘油三酯(TG)升高的发生率分 别为89.90%、69.72%、9.17%、41.28%,高胆固醇血症占51.37%,混合型高脂血症占39.45%;微小病变型肾病(MCD)、膜性肾病 (MN)、系膜增生性肾小球肾炎(MsPGN)、局灶阶段性肾小球硬化(FSGS)组间TC、TG、LDL-C、HDL-C 代谢异常发生率及代谢水平 比较均无明显差别(P>0.05);病理类型为MCD 及n-MCD 的PNS 患者,胆固醇水平均与24 小时尿蛋白定量呈正相关(r=0.440, P=0.036;r=0.361,P=0.001),与血白蛋白水平无明显相关性(P>0.05)。结论：成人PNS患者血脂代谢异常以TC 及LDL-C 升高为 主,临床分型中以高胆固醇血症及混合型高脂血症为主;病理类型为MCD及n-MCD 的PNS 患者,胆固醇水平均与24 小时尿蛋 白呈正相关,与血白蛋白水平无明显相关性。     

Effects of moderate riboflavin deficiency on lipid metabolism in rats

Dietary riboflavin intake of the people in Taiwan has been inadequate, while the fat intake has been increasing remarkably in recent years. Therefore, the effects of a moderate riboflavin deficiency on lipid metabolism in growing young rats fed diets containing 10, 25, or 40 percent calories of fat for 5 weeks were studied. The riboflavin deficiency status of the rats was certified by increased activity coefficients of erythrocyte glutathione reductase. Serum total lipids and cholesterol levels were significantly lower (P less than 0.05) in the medium fat-riboflavin deficient group. In the high fat-riboflavin deficient group, the growth and dietary intake were depressed and the liver weight/100 g body weight increased markedly (P less than 0.001). The liver total lipids, triglycerides, cholesterol and lipid peroxides of the high fat-riboflavin deficient group showed significant increases (P less than 0.025, P less than 0.025, P less than 0.05 and P less than 0.025 respectively), as compared with the pair-fed control groups. However, the increases were not significant in the medium fat and the low fat groups. The present study indicates that a high fat-riboflavin deficient diet would have adverse effects on lipid metabolism.     

血压、血脂、血糖、同型半胱氨酸及超敏C反应蛋白水平与脑梗死发病危险性的关系

目的:探讨血压、血脂、血糖、糖化血红蛋白、同型半胱氨酸(HCY)和超敏C反应蛋白(hs-CRP)与脑梗死发病危险性的相关性,为及时防止脑梗死的发病及早期诊断脑梗死提供理论依据。方法:采用回顾性病例对照研究,用全自动生化分析仪器检测各项生化指标,并运用SPSS 20.0软件包对256例脑梗死患者和216例健康对照者的血生化指标进行统计分析。同时,将脑梗死组分为三组:单纯脑梗死组、合并高血压组、合并糖尿病组,分别与正常对照组进行血脂水平的分析比较。结果:血压、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇酯(HDL-C)、同型半胱氨酸(HCY)、血糖、hs-CRP水平和总胆固醇/高密度脂蛋白胆固醇(TC/HDL-C)比值在病例组和对照组间有显著性差异(P0.05)。同时,在三组不同的病例组中血脂(TC、TG、LDL-C、TC/HDL-C)水平和HCY水平明显高于正常对照组,而HDL-C水平则明显低于对照组。(P0.05)。结论:高血压、高血糖、HCY、hs-CRP水平增高及血脂异常均与脑梗死发病危险性相关,联合检测上述指标对预防及治疗脑梗死均有重要意义。     

双歧杆菌对高胆固醇饮食小鼠血脂影响的研究

目的了解双歧杆菌对高胆固醇饮食水平异常的动物个体血脂及脂蛋白代谢的影响.方法将高胆固醇饮食小鼠分为2组,一组饮用双歧杆菌菌液,另一组常规饮水.经28 d喂养后,将全部动物处死,并立即取血,取上清液测定血脂及脂蛋白各项指标:血清总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白(HDL-C).结果高脂饮食 双歧杆菌组TG、TC水平显著低于高脂饮食组(P<0.01),HDL-C/TC显著高于高脂膳食组(P<0.01).结果表明灌胃双歧杆菌,小鼠血清中TC、TG浓度较高脂饮食显著降低(P＜0.01),同时HDL-C浓度有所增加.结论饮用双歧杆菌能显著改善高胆固醇饮食小鼠血脂及脂蛋白代谢状况.     

9758 例健康体检者血糖与血脂的关系分析

目的:探讨健康体检人群血糖与血脂现况及两者之间的相关性。方法:采集我院9758例健康体检者的空腹静脉血,检测其空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)水平,比较不同FPG水平组间各血脂水平,分析FPG水平与血脂的相关性。结果:各年龄组FPG、TC、TG、HDL-C和LDL-C水平差异均具有统计学意义(P0.05);FPG均与TC、TG和LDL-C水平呈现正相关(r=0.127,0.189,0.141,P0.005),而与HDL-C呈现负相关(r=-0.112,P0.005);根据FPG水平由高到低分为糖尿病(DM)组,血糖调节受损(IFG)组及血糖正常组,其中对TC和LDL-C水平异常率而言,IFG组DM组血糖正常组;对TG、HDL-C水平异常率而言,DM组IFG组血糖正常组。结论:健康人群中血糖和血脂水平呈现一定的相关性,两者的水平异常会增加慢性疾病的发生风险。     

Lipoprotein lipase activity is required for cardiac lipid droplet production

The rodent heart accumulates TGs and lipid droplets during fasting. The sources of heart lipids could be either FFAs liberated from adipose tissue or FAs from lipoprotein-associated TGs via the action of lipoprotein lipase (LpL). Because circulating levels of FFAs increase during fasting, it has been assumed that albumin transported FFAs are the source of lipids within heart lipid droplets. We studied mice with three genetic mutations: peroxisomal proliferator-activated receptor α deficiency, cluster of differentiation 36 (CD36) deficiency, and heart-specific LpL deletion. All three genetically altered groups of mice had defective accumulation of lipid droplet TGs. Moreover, hearts from mice treated with poloxamer 407, an inhibitor of lipoprotein TG lipolysis, also failed to accumulate TGs, despite increased uptake of FFAs. TG storage did not impair maximal cardiac function as measured by stress echocardiography. Thus, LpL hydrolysis of circulating lipoproteins is required for the accumulation of lipids in the heart of fasting mice.     

Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle.

Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile.     

Dietary L-arginine supplementation reduces abdominal fat content by modulating lipid metabolism in broiler chickens

This study investigated the effects of different levels of dietary L-arginine (L-Arg) supplementation on the abdominal fat pad, circulating lipids, hepatic fatty acid synthase (FAS) gene expression, gene expression related to fatty acid β-oxidation, and the performance of broiler chickens. We tested whether the dietary L-Arg levels affected the expression of genes related to lipid metabolism in order to reduce body fat deposition. A total of 192 broiler chickens (Cobb 500) aged 21 days with an average BW of 920 ± 15 g were randomly assigned to four groups (six broilers per replicate and eight replicates per treatment). The control group was fed a basal diet, whereas the treatment groups were fed basal diets supplemented with 0.25%, 0.50%, or 1.00% L-Arg for 3 weeks. The average daily feed intake, average daily gain and feed : gain ratio were not affected by the dietary L-Arg levels. However, chickens supplemented with L-Arg had lower abdominal fat content, plasma triglyceride (TG), total cholesterol (TC) concentrations, hepatic FAS mRNA expression and increased heart carnitine palmitoyl transferase1 (CPT1) and 3-hydroxyacyl-CoA dehydrogenase (3HADH) mRNA expression. These findings suggest that the addition of 0.25% L-Arg may reduce the plasma TC concentration by decreasing hepatic 3-hydroxyl-3-methylglutaryl-CoA reductase mRNA expression. This may lower the plasma TG and abdominal fat content by suppressing hepatic FAS mRNA expression and enhancing CPT1 and 3HADH (genes related to fatty acid β-oxidation) mRNA expression in the hearts of broiler chickens.     

Fucoxanthin-rich seaweed extract suppresses body weight gain and improves lipid metabolism in high-fat-fed C57BL/6J mice

An ethanol extract of fucoxanthin-rich seaweed was examined for its effectiveness as a nutraceutical for body fat-lowering agent and for an antiobese effect based on mode of actions in C57BL/6J mice. Animals were randomized to receive a semi-purified high-fat diet (20% dietary fat, 10% corn oil and 10% lard) supplemented with 0.2% conjugated linoleic acid (CLA) as the positive control, 1.43% or 5.72% fucoxanthin-rich seaweed ethanol extract (Fx-SEE), equivalent to 0.05% or 0.2% dietary fucoxanthin for six weeks. Results showed that supplementation with both doses of Fx-SEE significantly reduced body and abdominal white adipose tissue (WAT) weights, plasma and hepatic triglyceride (TG), and/or cholesterol concentrations compared to the high-fat control group. Activities of adipocytic fatty acid (FA) synthesis, hepatic FA and TG synthesis, and cholesterol–regulating enzyme were also lowered by Fx-SEE supplement. Concentrations of plasma high-density lipoprotein-cholesterol, fecal TG and cholesterol, as well as FA oxidation enzyme activity and UCP1 mRNA expression in epididymal WAT were significantly higher in the Fx-SEE groups than in the high-fat control group. CLA treatment reduced the body weight gain and plasma TG concentration. Overall, these results indicate that Fx-SEE affects the plasma and hepatic lipid profile, fecal lipids and body fat mass, and alters hepatic cholesterol metabolism, FA synthesis and lipid absorption.     

昆布（海带）对高脂血症大鼠血脂的调节作用和机制

目的：探讨昆布（海带）在实验性高脂血症大鼠中的降血脂作用和机制。方法：健康雌性Wistar大鼠40只,应用高脂饲料喂养方法建立高脂血症动物模型,海带粉饲料喂养干预治疗。生化法检测大鼠血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）水平。硫代巴比妥酸法和硝酸还原酶法分别检测脂质过氧化物丙二醛（MDA）和一氧化氮（NO）含量,黄嘌呤氧化酶法和化学比色法分别测定超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）活性。结果：经海带干预治疗后,动物血清TG、TC和LDL水平较模型组显著降低、HDL水平显著升高（P〈0.05）。治疗组动物血清和肝组织MDA和NO水平显著低于、而SOD和GSH-PX活性均显著高于模型组（P〈0.05）。结论：海带可能影响TG、TC、LDL和HDL等组分的代谢,通过增强抗氧化SOD和GSH-PX的活性,降低体内MDA和NO的水平,发挥调节血脂水平的作用。     

Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats

The aim of the study was to evaluate blood glucose and lipid lowering effects of Umbelliferone (UMB) in streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180 to 200 g) were induced diabetes by administration of STZ (40 mg/kg) intraperitonially. Normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had increased plasma glucose and decreased insulin, total proteins (TP), and albumin in addition to decreased food intake and body weight. Elevation in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL), and reduction in high density lipoprotein cholesterol (HDL-C) in the plasma were observed. Liver and kidney tissues of diabetic rats had elevation in the levels of TC, TG, FFA, and PL. Treatment with UMB decreased plasma glucose and increased insulin, TP, and albumin apart from food intake and body weight. In UMB-treated diabetic rats, plasma and tissue TC, TG, PL and FFA, and plasma LDL-C, VLDL-C, and HDL-C reversed to near normal. Thus, reduction of blood glucose and lipid profiles indicates that UMB has antidiabetic and antihyperlipidemic effects in diabetic rats.     

Biological and environmental sources of variation in plasma lipids and lipoproteins: the Jerusalem Lipid Research Clinic

We have previously described a general pattern of homogeneity in genetic and cultural determinants of blood lipids and lipoproteins among the major origin groups in the Israeli population. This paper reports on these determinants of total plasma cholesterol (TC), triglyceride (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and of the HDL-C/TC ratio, estimated from the total sample of 4,000 families whose members were examined in the Jerusalem Lipid Research Clinic. Both genetic (h2) and cultural (c2) components of inheritance were significant for all lipid variables. Under the most parsimonious model genetic heritability (h2) ranges from 0.45 for LDL-C, 0.47 for HDL-C to 0.64 for HDL-C/TC ratio. Cultural heritability (c2) was 0.03 for LDL-C, 0.04 for TC, 0.05 for TG and 0.07 for HDL-C and HDL-C/TC ratio. Within this population, as in others, genetic factors appear to be the major determinants of lipid variation, suggesting relative homogeneity of environmental correlates of plasma lipids.     

SCD-1基因过表达对鸭子宫上皮细胞钙离子和脂质含量的效应

硬脂酰辅酶A去饱和酶-1 (Stearoyl-CoA desaturase-1,SCD-1)是催化单不饱和脂肪酸合成的关键性蛋白酶,Ca~(2+)是生物体内重要阳离子,在生物体内发挥着重要作用。为探讨SCD-1基因与脂质指标和钙离子含量之间的关联性,通过构建pcDNA3.1(+)+SCD-1+Flag真核过表达载体和培养鸭子宫上皮细胞并共转染,通过载体上Flag标签检测SCD-1基因的过表达量,用Fluo-3/AM钙离子荧光标记法检测Ca~(2+)浓度,用脂质指标试剂盒检测细胞内的脂质含量。结果表明,鸭SCD-1基因过表达量与甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C)含量呈负相关,与Ca~(2+)浓度、总胆固醇(TC)含量、极低密度脂蛋白胆固醇(VLDL-C)含量和低密度脂蛋白胆固醇(LDL-C)含量呈正相关;Ca~(2+)与TG、LDL-C和HDL-C的含量呈正相关,与TC和VLDL-C含量呈负相关,研究结果揭示了SCD-1基因过表达能够调控鸭子宫上皮细胞中Ca~(2+)浓度和脂质合成与转运。     

Enterocyte-specific ATGL overexpression affects intestinal and systemic cholesterol homeostasis

Enterocytes of the small intestine (SI) play an important role in maintaining systemic lipid levels by regulating dietary lipid absorption and postprandial lipoprotein secretion. An excessive amount of dietary-derived triglycerides (TGs) taken up by the apical side of enterocytes or basolaterally internalized lipoprotein remnants can be transiently stored in cytosolic lipid droplets (cLDs). As mice lacking adipose TG lipase (ATGL) in the SI display massive accumulation of cLDs but also delayed cholesterol absorption, we hypothesized that SI-specific overexpression of ATGL (Atgl iTg) might have beneficial effects on lipid homeostasis in the gut and possibly throughout the body. Here, we demonstrate that Atgl iTg mice had only modestly increased enzymatic activity despite drastically elevated Atgl mRNA levels (up to 120-fold) on chow diet, and was highly induced upon high-fat/high-cholesterol diet (HF/HCD) feeding. Atgl iTg mice showed markedly reduced intestinal TG concentrations after acute and chronic lipid challenge without affecting chylomicron TG secretion. Circulating plasma cholesterol levels were significantly lower in Atgl iTg mice under different feeding conditions, contrasting the accelerated uptake of dietary cholesterol into the circulation after HF/HCD feeding. In the fasted state, gene expression analysis revealed modulation of PPARα and liver X receptor (LXR) target genes by an increased fatty acid release, whereas the decreased plasma cholesterol concentrations in refed mice were more likely due to changes in HDL synthesis and secretion. We conclude that ATGL, in addition to its role in TG catabolism, plays a critical role in whole-body cholesterol homeostasis by modulating PPARα and LXR signaling in intestinal enterocytes.