脂蛋白脂酶基因与代谢综合征关系的研究进展

脂蛋白脂酶是脂质代谢的关键酶之一,是血浆中清除甘油三酯的限速酶,主要催化乳糜微粒和极低密度脂蛋白核心中的甘油三酯水解,使得机体能够利用由食物摄取和肝脏合成的脂肪,同时释放出脂肪酸和单酰甘油.脂蛋白脂酶基因突变可以影响脂蛋白脂酶的活性,从而导致脂代谢紊乱,与肥胖、胰岛素抵抗、2型糖尿痛和高血压的发病风险相关.本文综述了脂蛋白脂酶的结构、功能、基因结构及其多态性与血脂和代谢综合征关系的研究进展.     

脂蛋白脂酶与肥胖

脂蛋白脂酶(lipoprotein lipase,LPL)是甘油三酯分解代谢的限速酶,与肥胖发生联系密切.综述了LPL蛋白的分子结构特点、分泌方式,及其参与的与肥胖发生有关的脂肪细胞分化、脂质沉积、脂代谢等过程.     

脂蛋白脂酶基因的研究进展

脂蛋白脂酶(lipoprotein lipase, LPL)是脂质代谢的关键酶, 主要催化乳糜微粒和极低密度脂蛋白中的甘油三酯水解, 产生供组织利用的脂肪酸和单酰甘油。LPL基因突变影响LPL活性, 导致脂质代谢紊乱, 与2型糖尿病、高血压、动脉硬化、肥胖、冠心病的发病风险相关联。文章综述了LPL基因的结构、功能、表达调控以及与复杂疾病的关联研究进展。     

脂蛋白脂酶调控因子研究进展

脂蛋白脂酶(Lipoprotein lipase, LPL)是脂质代谢的关键酶, 其正常调控对于机体向组织提供脂质营养至关重要。作为LPL重要的调控因子, 糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(Glycosylphosphatidylinositol- anchored high density lipoprotein-binding protein 1, GPIHBP1)能与LPL结合起脂解平台的作用, 并作为载体参与LPL向毛细血管内皮细胞的转运。另外, 近年来也鉴定出其他几个LPL活性调控因子, 包括microRNAs、A型重复排序蛋白相关受体(Sortilin-related receptor with A-type repeats, SorLA)和载脂蛋白(Apolipoproteins, apo)。这些LPL调控因子的成功鉴定, 有助于人们深入认识机体脂解代谢和乳糜微粒血症发生的内在机制。文章重点综述了LPL的调控因子GPIHBP1的研究进展, 同时也对其他几个调控因子的研究进展进行了讨论。     

脂蛋白酯酶与动脉粥样硬化

脂蛋白酯酶(1ipopmtein lipase,LPL)是调节脂蛋白代谢的一种关键酶,如具有水解血浆脂蛋白中三酰甘油的作用等．体内LPL减少会导致血三酰甘油升高和高密度脂蛋白胆固醇降低,增加患动脉粥样硬化的危险．通过提高LPL的活性可以抑制动脉粥样硬化的发生发展．已有的研究说明NO-1886促进心肌和脂肪组织LPL mRNA表达,提高心肌、脂肪组织、骨骼肌和血液中LPL活性,因而改善脂蛋白代谢,抑制动脉粥样硬化．     

脂蛋白脂酶基因多态性与2 型糖尿病的相关性研究

目的：探讨脂蛋白脂酶（lipoprotein lipase,LPL）基因PvuⅡ酶切多态性与2型糖尿病的相关性。方法：采用聚合酶链反应-限制性片段长度多态性（PGR-RFLP）方法,分析了156例样本LPL基因第6内含子PvuⅡ多态性（病例组98人。对照组58。其中40个2型糖尿病同胞对,病例组40人,对照组40人）。结果：病例组与对照组的基因型和基因频率均无显著性差异。结论：湖北汉族人群脂蛋白脂酶基因PvuⅡ酶切多态性与2型糖尿病无明显关联。     

鳜脂蛋白脂酶基因SNP及其与食性驯化相关性分析

鳜食性奇特,通常情况下拒食死饵或配合饲料,在长期的养殖过程中发现:通过驯养,能逐步诱导部分鳜以非活饵为食。通过分子标记定向选育易驯化鳜并使用人工饲料大规模养殖,可以有效解决鳜养殖中存在的成本高、污染严重、病害严重等问题。脂蛋白脂酶基因(Lipoprotein lipase LPL)是脂蛋白代谢的关键酶之一,生理功能是将乳糜微粒和极低密度脂蛋白核心的甘油三酯催化分解为甘油和脂肪酸,以供组织氧化供能和贮存。文章采用PCR产物直接测序法对鳜脂蛋白脂酶基因6、7内含子和6、7、8外显子进行了SNPs遗传多态性检测和分析,探寻LPL基因的等位基因及其基因型在两个食性驯化表型群体中的分布情况。结果在第7外显子处共检测到3个SNPs位点(A25T、G26T和C29G),其中A25T、C29G两个为非同义突变。利用卡方检验分析驯化与未驯化组,结果表明LPL基因3个SNPs位点对鳜的食性驯化不具显著差异性(P>0.05)。将3个SNPs位点不同基因型组合成5种双倍型,卡方检验表明双倍型Dip2在两组中存在显著差异(P<0.05)。文章成功完成鳜LPL基因组部分区段多态性分析,因而可以考虑将LPL基因作为影响鳜食性驯化的候选基因,作为遗传标记,为今后的标记辅助选择育种工作奠定基础,具有广泛的应用前景。     

中华鲟及六种淡水养殖鱼类脂蛋白脂酶和肝脂酶基因克隆及系统进化分析

为了研究鱼类脂蛋白脂酶(1iportein lipase,LPL)、肝脂酶(hepatic lipase,HL)基因结构、功能及分子系统关系,作者克隆了中华鲟(Acipenser sinensis)、鲢(Hypophthalmichthys molitrix)、鳙(Aristichthys nobilis)、草鱼(Ctenopharyngodon idellus)、鲮鱼(Cirrhinus molitorella)、尼罗罗非鱼(Oreochromis niloticus)和斑鳢(Channa maculata)的LPL和HL基因cDNA核心序列,并推测了其相应氨基酸序列.同时,还应用5'RACE和3'RACE技术分别扩增中华鲟、鲢肝脏LPL基因与中华鲟肝脏HL基因cDNA全序列.序列同源性分析表明,LPL和HL氨基酸序列分别在哺乳类动物、鸟类、鱼类中相对保守.与已知的脊椎动物内皮脂酶(endothelial lipase,EL)和胰脂酶(pancreatic 1ipase,PL)氨基酸序列构建系统进化树,发现LPL、HL、EL与PL同属脂肪酶家族,四者聚集成一有根树.     

脂蛋白脂酶基因与apo C—Ⅱ基因变异

原发性高甘油三酯血症是由于血浆中的甘油三酯持续升高,达到了一个高水平而赞成的一组症侯,甘油三酯代谢紊乱的病人往往带有家族性,提示某些基因的遗传缺陷可能是导致高甘油三酯血症的原因之一,具有常染色体隐性遗传特性,引起家族性乳糜微粒血症的两个主要因素是脂蛋白脂酶（LPL）以及LPL的协同因子载脂蛋白C－Ⅱ（apo C－Ⅱ）的异常,对于这些基因变异目前已经有了比较成熟的检验方法,但是基因治疗的治疗尚处在研究阶段。     

脂蛋白脂酶基因的克隆、序列测定及定点突变

 以人的脂肪组织总RNA为模板 ,参考已报道的脂蛋白脂酶 (lipoproteinlipase ,LPL)cDNA设计引物 ,利用RT PCR方法扩增得到了LPLcDNA ,并经序列测定证实其序列是正确的 .在冠心病患者LPL基因第 5外显子的 830位碱基处发现了G→A的转换 ,该变异导致LPL基因第 192位的密码子CGA被CAA取代 ,使LPL第 192位精氨酸改变为谷氨酰胺 .在变异碱基附近设计合成两条引物 ,其中一条包含所要改变的碱基 ,利用基于PCR的定点突变技术和体外重组的方法获得了G830A变异的LPLcDNA     

哺乳动物脂蛋白脂肪酶基因的进化研究

脂蛋白脂肪酶(LPL)是脂肪细胞、心肌细胞、骨骼肌细胞、乳腺细胞以及巨噬细胞等实质细胞合成和分泌的一种糖蛋白,其生理功能为促进乳糜微粒和极低密度脂蛋白中甘油三脂(TG)的分解,此外,lpl基因的异常可导致血TG水平的升高和高密度脂蛋白胆固醇(HDL-C)水平的降低,导致冠状动脉粥样硬化等疾病的形成和发展。采用生物信息学手段来分析在不同哺乳动物中lpl基因的长度多态性、终止密码子多态性、ORF多态性以及氨基酸序列的同源性,建立不同哺乳动物lpl基因上的进化关系图谱,为了解哺乳动物脂蛋白脂肪酶基因的演化关系,研究该基因的作用机理提供资料。     

Comparative Analyses of Lipoprotein Lipase,Hepatic Lipase,and Endothelial Lipase,and Their Binding Properties with Known Inhibitors

The triglyceride lipase gene subfamily plays a central role in lipid and lipoprotein metabolism. There are three members of this subfamily: lipoprotein lipase, hepatic lipase, and endothelial lipase. Although these lipases are implicated in the pathophysiology of hyperlipidemia and atherosclerosis, their structures have not been fully solved. In the current study, we established homology models of these three lipases, and carried out analysis of their activity sites. In addition, we investigated the kinetic characteristics for the catalytic residues using a molecular dynamics simulation strategy. To elucidate the molecular interactions and determine potential key residues involved in the binding to lipase inhibitors, we analyzed the binding pockets and binding poses of known inhibitors of the three lipases. We identified the spatial consensus catalytic triad “Ser-Asp-His”, a characteristic motif in all three lipases. Furthermore, we found that the spatial characteristics of the binding pockets of the lipase molecules play a key role in ligand recognition, binding poses, and affinities. To the best of our knowledge, this is the first report that systematically builds homology models of all the triglyceride lipase gene subfamily members. Our data provide novel insights into the molecular structures of lipases and their structure-function relationship, and thus provides groundwork for functional probe design towards lipase-based therapeutic inhibitors for the treatment of hyperlipidemia and atherosclerosis.     

Gender Differences in Lipoprotein Lipase Activity after Acute Exercise

Objective: To determine whether gender differences exist in lipoprotein lipase (LPL) activity in response to exercise and/or insulin. Exercise and insulin are known modulators of LPL activity in men, but this is less clear in women. LPL activity may predict propensity for obesity; therefore, understanding its modulators is of considerable importance. Research Methods and Procedures: Gender differences in skeletal muscle and adipose tissue LPL activity were determined after a single bout of exercise followed by a hyperinsulinemic/euglycemic clamp and compared with an identical rest day in healthy lean men (n = 10) and women (n = 10). Muscle and adipose tissue biopsies were obtained pre‐ (post‐exercise vs. rest) and post‐clamp. Results: Basal levels of muscle and adipose tissue LPL activity were not different between men and women. There was, however, a significant gender by day interaction for muscle LPL activity (p = 0.023) and adipose tissue LPL activity (p = 0.013). In muscle, this was because of a significant increase in LPL activity on the exercise vs. rest day in men (p < 0.001) but not women. Adipose tissue LPL activity also increased significantly in men on the exercise day relative to rest day (p = 0.04) but decreased in women (p = 0.10). The hyperinulinemic/euglycemic clamp had no independent effect on tissue LPL activity, in either gender, after rest or exercise. Discussion: In the 3 to 4 hours after exercise, muscle and adipose tissue LPL activity increased significantly in men, whereas LPL activity remained unchanged in women.     

Preparation of a Homogenous and Stable form of Bovine Milk Lipoprotein Lipase

Abstract

Lipoprotein lipase was purified to homogeneity from bovine skim milk by a two-step procedure using chromatography on heparin-Sepharose. As determined by gradient-polyacrylamide gel electrophoresis in sodium dodecyl sulfate, purified lipoprotein lipase showed a single band with an apparent molecular weight of 55,000. The use of Triton N-101 in the washing buffers was the major improvement from previously reported purification procedures that resulted in a stable homogeneous preparation of the enzyme.