Implication of lipoprotein lipase-deficient impaired learning and memory: focus on aging and testosterone deficiency

OBJECTIVE Normal male aging is associated with declines in levels of the sex steroid hormone testosterone. A large body of evidence supports a neurotrophic role for testosterone in central nervous system. Lipoprotein lipase(LPL) is also expressed in the brain with highest levels found in the pyramidal cells of the hippocampus, we previous reported LPL-deficient mice exhibited memory disfunction. Testosterone is known to be largely converted to estradiol following aromatization within the hippocampus. Although testosterone has been implicated in lipid metabolism, it remains elusive whether testosterone can regulate brain LPL through DNA methylation mechanism. In order to clarify DNA methylation control exerted by testosterone over LPL gene in central nervous system, and its effect on lipid metabolism, we examined the adult male rat hippocampus to determine whether castration induced testosterone deficiency can affect lipid profile and LPL gene expression through its altered methylation pattern. METHODS Model of aging with declines in levels of the sex steroid hormone testosterone was performed as our previous description. RESULTS(1) Serum testosterone and brain testosterone levels were significantly decreased, which were restored to the control level after testosterone replacement,respectively(P<0.01);(2) Androgen deficiency was not found in Morris water maze and motor performance, however, androgen deficiency increases neurological and cognitive impairment in aged rats.(3)Decreased expression of olfactory marker protein(OMP) in olfactory bulb of SD rats treated with androgen deficiency.(4) The expression of Fox O3 and OMP in the olfactory bulb of androgen deficient rats was down-regulated, accompanied by dysfunction of the olfactory limbic system.(5) Decreased LPL m RNA level and inversely increased LPL promoter methylation level were observed following androgen deficiency and reserved by testosterone replacement.(6) In contrast, androgen deficiency slightly increased estrogen receptor beta(ERβ) m RNA levels and significantly decreased its promoter methylation levels within the hippocampus, and reserved as well by testosterone replacement. CONCLUSION(1) LPL in synaptic plasticity and contributes to a better understanding of the LPL function in the brain, where altered LPL levels are related to learning and memory impairment.(2) Androgen and Fox O3 play an important role in the olfactory cognitive process of the nervous system.(3) LPL expression in hippocampus is actively maintained by sex steroid hormones and that DNA methylation modification may contribute to this homeostatic regulation.

Genetic Screening of the Lipoprotein Lipase Gene for Mutations in Chinese Subjects with or without Hypertriglyceridemia

Objective： To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia （HTG）. Methods： The lipoprotein lipase （LPL） gene was screened for mutations in 386 Chinese subjects with （108 cases in the HTG group） or without HTG （278 cases in the control group）, by single-strand conformation polymorphism （SSCP） analysis and DNA sequencing. Results： One novel silent mutation L103L, one missense mutation P207L, three splicing mutations Int3/3＇ -ass/C（-6）→T, and the common S447X polymorphism has been identified in the whole coding region and exon-intron junctions of the LPL gene were examined. Heterozygous P207L found in the HTG group was the first case reported in Asia and subsequently another P207L heterozygote was found in the proband＇s family, all of which suggested that P207L was one of the causes of familial combined hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3＇-ass/C（-6）→T was found in both groups in the present study although it was regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial polymorphism S447X, there was also some supportive evidence that the levels of triglycerides （TG） in S447X carriers were significantly lower than noncarders in the subjects without HTG. Conclusions： The association between the LPL variants and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale screening should be necessary and justifiable.

Impact of serum levels of lipoprotein lipase, hepatic lipase, and endothelial lipase on the progression of coronary artery disease

Purpose: The purpose of this study was to investigate the relationship between serum levels of lipoprotein lipase(LPL), hepatic lipase(HL), and endothelial lipase(EL) and the progression of coronary artery disease(CAD).Materials and methods: According to the inclusion criteria, exclusion criteria, diagnostic criteria, angiography results, and the random matching scheme, the enrolled patients were divided into the following two groups: the progression-free group(n ? 47) and the progression group(n ? 15). The baseline characteristics and various biochemical parameters were obtained from the medical records and medical history. Serum LPL, HL, and EL levels were detected by ELISA. The correlation between serum LPL, HL, and EL levels and coronary lesions was statistically analyzed with SPSS software.Results: Significant differences were observed in serum levels of HL and EL between the progression-free group and the progression group(HL, 75.5 ? 39.2 ng/mL vs. 125.1 ? 42.1 ng/mL, P < 0.05;EL, 139.2 ? 59.6 pg/mL vs.175.1 ? 40.1 pg/mL, P < 0.05), while the difference in the LPL level was not significant(P > 0.05). Receiver operating characteristic curve(ROC) analysis showed that the area under the curve(AUC) values of LPL, HL, and EL were 0.506(95% CI: 0.369–0.642, P ? 0.9470), 0.792(95% CI: 0.664–0.888, P < 0.0001), and 0.693(95% CI:0.553–0.811, P ? 0.0095), respectively. Additionally, logistic regression analysis showed that the serum level of HL was an independent risk factor for coronary artery lesion progression.Conclusion: Serum levels of EL and HL, but not the serum level of LPL, were positively correlated with the progression of CAD. The serum level of HL was an independent risk factor for the progression of CAD, while the serum level of EL or LPL was not an independent risk factor for the progression of CAD. For the diagnosis of CAD progression, the serum level of HL was better than the serum level of EL or LPL.

POLYMORPHISMS OF THE HUMAN LIPOPROTEIN LIPASE GENE:POSSIBLE ASSOCIATION WITH LIPID LEVELS IN PATIENTS WITH CORONARY HEART DISEASE IN BEIJING AREA

The polymorphisms(Pvu Ⅱand Hind Ⅲ) on the lipoprotein lipase(LPL) gene locus was investigated in a sample of 100 patients surviving previous myocardial infarction and 100 age matched healthy individuals selected from Han Chinese of Beijing area.In patient group a strong association was found between H+allele of Hind Ⅲ polymorphism and raised TG levels(P<0.01).In control group P-P-genotype was observed to be associated with higher TG levels compared with P+P genotype of Pvu Ⅱ polymorphism(P<0.05).Combination of H+H+ genotype with P-P-genotype showed the highest TG levels among all nine kinds of genotype combinations in patient group(P<0.01).However,comparison of distribution of alleles and genotypes of these polymorphisms between patient group and control group demonstrated no significant difference. Our data suggest that the polymorphisms at the LPL gene,as the linkage markers with an aetiologic mutation at or around LPL gene,may constitute one of the genetic determinants for the population variation in plasma TG levels,as well as for the common dyslipidemia in Chinese population.

Establishment of Real-Time TaqMan-Fluorescence Quantitative RT-PCR Assay for Detection and Quantification of Porcine Lipoprotein Lipase mRNA

Porcine lipoprotein lipase （LPL） cDNA was cloned as the standard for real-time quantifying LPL mRNA and the TaqMan-fluorescence quantitative PCR assay for detection was established. The total RNA extracted from Longissimus dorsi of porcine was reverse-transcribed to cDNA. LPL cDNA was ligated with pGM-T vector and transformed into Escherichia coli TOP10. Plasmid DNA extracted from positive clones was verified by PCR amplification and sequenced. LPL was amplified by real-time fluorescence quantitative PCR from the plasmid DNA. The concentration of DNA template purified was detected by analyzing absorbance in 260 nm and then the combined plasmid was diluted to series as standard for fluorescence quantitative PCR （FQ-PCR）. The method of LPL mRNA real-time PCR was well established, which detected as low as 103 with the linear range 10^3 to 10^10 copies. The standard curves showed high correlations （R2 = 0.9871）. A series of standards for real-time PCR analysis have been constructed successfially, and real-time TaqMan-fluorescence quantitative RT-PCR is reliable to quantitatively evaluate FQ-PCR mRNA in L. dorsi of porcine.

Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis

AIM： To examine the influence of lipoprotein lipase （LPL） gene polymorphism in ulcerative colitis （UC） patients.METHODS： Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind Ⅲ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing. Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.RESULTS： In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype （OR = 3.13, 95% CI = 0.95-10.33）. Patients with H^＋/- or H^-/- genotype for Hind Ⅲ polymorphism also were more nu merous than those with H^＋/＋ genotype （OR = 2.51, 95% CI = 0.85-7.45）. In the group with H^＋/＋ genotype for Hind Ⅲ polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H^＋/- or H^- genotype （P 〈 0.01, OR = 6.46, 95% CI = 1.39-30.12）. Hypertriglycemia was also more prevalent in patients with P^＋/＋ genotypes for Pvu Ⅱ polymorphism （P 〈 0.05, OR = 3.0, 95% CI = 1.06-8.50）. Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.

Effect of Homogenization Temperature and Pressure on Lipoprotein Lipase Activity and Free Fatty Acids Accumulation in Milk

This study demonstrated that homogenization did not increase the activity of lipoprotein lipase (LPL) in spite of a fast accumulation of free fatty acids (FFA). Two homogenization pressures (100 and 170 bar) and two temperatures (40℃and 50℃) were examined. The activity of LPL was analyzed and the formation of FFA was measured with two different methods, the B.D.I.-method and a nonesterified fatty acids (NEFA) method. A homogenization temperature of 50℃ resulted in a decreased LPL activity compared to 40℃. No effect of homogenization pressure was found. Analyzing FFA concentration with the B.D.I.-method resulted in significant effect of homogenization temperature and no effect of pressure. The largest formation of FFA was found in milk homogenized at 40℃. Using the NEFA method, another result was obtained, indicating no effect of homogenization temperature and a larger FFA accumulation at 100 bar than at 170 bar. Both analytic methods demonstrated significant production of FFA during 60 min incubation at homogenization temperature after treatment. The level of FFA in the milk samples immediately after homogenization was very high, demonstrating that LPL cleaves the triglycerides very rapidly when the native membrane was damaged. The regression between the B.D.I.-method and the NEFA was fair in the interval between 4 and 14 mmol/100 g fat, whereas at higher concentrations, the correlation was poor.

Correlation between betatrophin/angiogenin-likeprotein3/lipoprotein lipase pathway and severity of coronary artery disease in Kazakh patients with coronary heart disease

BACKGROUND The results of previous animal experiments and clinical studies have shown that there is a correlation between expression of betatrophin and blood lipid levels.However,there are still differences studies on the correlation and interaction mechanism between betatrophin,angiogenin-likeprotein3(ANGPTL3)and lipoprotein lipase(LPL).In our previous studies,we found an increase in serum ANGPTL3 Levels in Chinese patients with coronary heart disease(CHD).Therefore,we retrospectively studied Kazakh CHD patients.AIM To explore the correlation between the betatrophin/ANGPTL3/LPL pathway and severity of coronary artery disease(CAD)in patients with CHD.METHODS Nondiabetic patients diagnosed with CHD were selected as the case group;79 were of Kazakh descent and 72 were of Han descent.The control groups comprised of 61 Kazakh and 65 Han individuals.The serum levels of betatrophin and LPL were detected by enzyme-linked immunosorbent assay(ELISA),and the double antibody sandwich ELISA was used to detect serum level of ANGPTL3.The levels of triglycerides,total cholesterol,and fasting blood glucose in each group were determined by an automatic biochemical analyzer.At the same time,the clinical baseline data of patients in each group were included.RESULTS Betatrophin,ANGPTL3 and LPL levels of Kazakh patients were significantly higher than those of Han patients(P=0.031,0.038,0.021 respectively).There was a positive correlation between the Gensini score and total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),betatrophin,and LPL in Kazakh patients(r=0.204,0.453,0.352,0.471,and 0.382 respectively),(P=0.043,0.009,0.048,0.001,and P<0.001 respectively).A positive correlation was found between the Gensini score and body mass index(BMI),TC,TG,LDL-C,LPL,betatrophin in Han patients(r=0.438,0.195,0.296,0.357,0.328,and 0.446 respectively),(P=0.044,0.026,0.003,0.20,0.004,and P<0.001).TG and betatrophin were the risk factors of coronary artery disease in Kazakh patients,while BMI and betatrophin were the risk factors in Han patients.CONCLUSION There was a correlation between the betatrophin/ANGPTL3/LPL pathway and severity of CAD in patients with CHD.

Lipoprotein lipase and obesity

Obesity is one of the fast-growing major diseases in developed and developing countries. As has been persuasively argued, long-term imbalance between intake and expenditure of fat is a central factor in the etiology of obesity. Obesity aggravates insulin resistance and promotes cardiovascular diseases and atherosclerosis. We hypothesized that elevating lipoprOtein lipase (LPL) activity in skeletal muscle would cause an improvement of obesity. To test this hypothesis, we studied the effects of the LPL activator NO-1886 inobese animals. NO-1886 elevated LPL activity in skeletal muscle, and improved obesity as well as insulin resistance in obese rats. Furthermore, NO-1886 mitigated body weight gain induced by pioglitazone without suppressive effect on the adiponectin-increasing action of pioglitazone. LPL activators hold a lot of promise of curing several diseases shown above in clinical scene.

Effect of Lipoprotein Lipase Gene Polymorphism on Plasma Lipid Levels, BMI and Subcutaneous Fat Distribution in Simple Obesity Children

Objective To study the effects of Hind Ⅲ DNA polymorphism in the lipoprotein lipase (LPL)gene on plasma lipid levels, body mass index (BMI) and subcutaneous fat distribution in simple obesity children.Methods The LPL Hind Ⅲ genotypes were detected with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in 92 children with simple obesity. The levels of the plasma lipid, plasma lipoproteins, BMI and skinfold thickness in three regions (biceps, subscapular and abdominal wall) were also measured. Results It was shown that the levels of TG, TC, LDL C, ApoB, BMI, biceps and subscapular skinfold thickness, and the average value of the skinfold thickness in three regions were significantly higher in the obese children with H+H+ genotype than those with H+H-genotype. Conclusions It can be concluded that LPL Hind Ⅲ polymorphism may modify the levels of plasma lipid, plasma lipoprotein and BMI in children with simple obesity, and meanwhile alters the distribution of subcutaneous fat.

Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer

Background:Lymph node metastasis(LNM)is the primary mode of metastasis in gastric cancer(GC).However,the precise mechanisms underlying this process remain elusive.Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis,yet the role of lipoprotein lipase(LPL),a pivotal enzyme involved in exogenous lipid uptake,remains uncertain in tumor metastasis.Therefore,the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process.Methods:Intracellular lipid levels were quantified using oil red O staining,BODIPY 493/503 staining,and flow cytometry.Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown.Protein expression levels were assessed through immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assays.The mouse popliteal LNM model was utilized to investigate differences in LNM.Immunoprecipitation and mass spectrometry were employed to examine protein associations.In vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4(ANGPTL4)phosphorylation.Results:We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive(N+)GC and further demonstrated that a high-fat diet can expedite LNM.LPL was found to be significantly overexpressed in N+GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells.Leptin,an obesity-related hormone,intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage.Circulating leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1(IRE1)kinase,leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL.Moreover,our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid,which then triggered the cyclooxygenase-2/prostaglandin E2(PGE2)pathway,thereby promoting tumor lymphangiogenesis.Conclusions:Leptin-induced phosphorylation of ANGPTL4 facilitates LPLmediated lipid uptake and consequently stimulates the production of PGE2,ultimately facilitating LNM in GC.

Relationship between a novel polymorphism of lipoprotein lipase gene and coronary heart disease

OBJECTIVE: To investigate polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relationship between these polymorphisms in LPL gene and CHD. METHODS: Genomic DNA was extracted from patients with CHD and normal control subjects using a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products were detected by denaturing high-performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. RESULTS: A novel polymorphic site, G830A, that is within the fifth exon of the LPL gene was found. The 192 codon CGA was changed into CAA and resulted in the substitution of glutamine for arginine. Between the control and CHD groups, chi-square test showed no significant difference in the frequencies of the A/A genotype and A allele (P > 0.05). However, the frequencies of A/A genotype and A allele (0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma high density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P Gln substitution polymorphism and CHD, but there is a significant positive correlation between the A/A genotype of the LPL gene and CHD associated with high triglyceride/lowed high density lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.

Hypotriglyceridemic Effects of Apple Polyphenols Extract via Up-Regulation of Lipoprotein Lipase in Triton WR-1339-Induced Mice

Objective：To investigate the anti-hyperlipidemic effects of apple polyphenols extract（APE）in Triton WR-1339-induced endogenous hyperlipidemic model.Methods：Firstly,APE was isolated and purified from the pomace of Red Fuji Apple and contents of individual polyphenols in APE were determined using highperformance liquid chromatography-mass spectrometry（HPLC-MS）.Secondly,forty male National Institude of Health（NIH）mice were randomly divided into 5 groups with 8 animals in each group.The Fenofibrate Capsules（FC）group and APE groups received oral administration of respective drugs for 7 consecutive days.All mice except those in the normal group were intravenously injected through tail vein with Triton WR-1339 on the6th day.Serum and livers from all the mice were obtained 18 h after the injection.The changes in serum total cholesterol（TC）,triglyceride（TG）,lipoprotein lipase（LPL）and hepatic triglyceride lipase（HTGL）were measured by respective kits.Finally,expression of hepatic peroxisome proliferator-activated receptor alpha（PPARα）mRNA was measured by real-time reverse transcription-polymerase chain reaction（RT-PCR）method.Results：Serum TC and TG levels significantly increased in Triton WR-1339-induced model group compared with the normal group（P〈0.01）.Oral administration of APE[200 and 400 mg/（kg·day）]dose-dependently reduced the serum level of TG in hyperlipidemic mice（P〈0.01）.Serum LPL and HTGL activities significantly decreased in Triton WR-1339-induced model group compared with the normal group（P〈0.05）.Oral administration of APE[200 and 400 mg/（kg·day）]dose-dependently elevated the serum activity of LPL in hyperlipidemic mice（P〈0.05or P〈0.01）.Furthermore,compared with the normal group,hepatic mRNA level of PPARαin the model group significantly decreased（P〈0.01）.Oral administration of APE[200 and 400 mg/（kg·day）]dose-dependently elevated the expression of PPARαin hyperlipidemic mice（P〈0.05 or P〈0.01）.Conclusion：APE could reduce TG level via up-regulation of LPL activity,which provides new evidence to elucidate the anti-hyperlipidemic effects of APE.

Knockout of lipoprotein lipase with CRISPR/Cas9 causes severe developmental defects and affects lipid deposition in Japanese medaka(Oryzias latipes)

In mammals,lipoprotein lipase(LPL)has been found to play an important role in lipid mentalismand deposition.LPL deficiency in humans(Homo sapiens)and mice(Mus musculus)tends to cause hypertriglyceridemia.The lpl gene is not expressed in adult mammalian liver,but is in adult fish liver.The functions provided by the lpl gene are diverse in vertebrates.Here,we knocked out the lpl gene in Japanese medaka(Oryzias latipes)with the CRISPR/Cas9 system.The lpl-knockout(KO)homozygous individuals showed severe developmental defects with an extremely emaciated and deformedbody and onlyaccounted for about5%of the F2fish.This is consistentwiththefindings inmicebut disaccords with the results for zebrafish(Danio rerio).Compared with wild-type(WT)madaka,the mRNA level of lpl in lpl-KO heterozygous mutant was significantly higher in the muscle,showed no significant difference in the liver,and was significantly lower in the heart.Under lpl heterozygous deficiency,the relative area of Oil RedO and triglycerides(TG)level in the liver,heart and muscle tissue covaried with levels of lpl mRNA in medaka.The lpl heterozygous deficiency did not affect the levelsofTG,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and total cholesterol(TC)in the plasma of medaka,which is inconsistent with the findings in mammals.In general,the lpl gene plays an important role in the growth and development and is closely related to lipid deposition of medaka.

Effect of Astragalus-Angelica Mixture on Lipoprotein Lipase and Lecithin-Cholesterol Acyltransferase of Nephrotic Rats

Objective: To investigate the mechanism of Astragalus-Angelica Mixture (AAM) ’s effects on lipid metabolism disturbance in nephrotic rats.Methods: To examine the effects of AAM on serum albumin, lipid levels, and activities of lipoprotein lipase (LPL) and lecithin-cholesterol acyltransferase (LCAT), which are key enzymes for metabolism of lipid in immune-induced nephrotic hyperlipidemia rats and exogenous hyperlipidemia rats.Results: In nephrotic rats, serum albumin was reduced, lipid increased significantly, LPL activity decreased markedly and the LCAT activity was relatively insufficient. Activities of LPL and LCAT increased obviously in AAM treated nephrotic rats. There were no change of activities of LPL and LCAT in exogenous hyperlipidemia rats and AAM showed no effect on the activities of these two enzymes.Conclusion: The effect of AAM on regulating lipid metabolism might be due to enhance the clearance of both triglyceride-rich and cholesterol-rich apoB containing lipoprotein by improving the activities of LPL and LCAT.

Apolipoprotein A-V gene therapy for disease prevention/treatment:a critical analysis

Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.

Adaption of a commercial lipase kit to measure bile salt-stimulated lipase in human milk

A highly sensitive,fluorometric method for measuring activities of two major lipases in milk,lipoprotein lipase(LPL)and bile salt-stimulated lipase(BSSL)is described.Human milk LPL showed linear activity from 65 to 347 U/L(U=1μmol/min)and the quantification limit was theoretically about 65 U/L.For human milk BSSL,the linear range was from 10 to 267 U/L and the quantification limit was 18 U/L.The mean LPL and BSSL activities were 409±13 U/L and 5263±132 U/L,respectively.This corresponded well to the values reported in literature.The residual LPL and BSSL activities were reduced dramatically to 21%,and 2%,respectively,when the milk was heated to 55°C;heating to 50°C caused only nominal reductions of LPL and BSSL(activities remaining∼82%and 87%,respectively).No BSSL activity was detected in cow,camel,goat milk or in infant formula.

脂代谢相关蛋白在恶性肿瘤中的表达及关系研究

脂代谢紊乱和肥胖是乳腺癌、结直肠癌、卵巢癌等多种恶性肿瘤的高危因素。脂质能为癌细胞的增殖、迁移及侵袭提供生物膜合成的原料、营养成分、信号分子、能量支持。脂代谢过程中关键酶表达异常,是脂代谢重编程的主要表现。本文综述脂肪酸从头合成相关酶、脂肪酸摄取转运蛋白、脂质水解和动员相关酶及脂肪酸氧化相关酶的临床研究进展,从代谢层面探索恶性肿瘤的发病机制、寻找治疗新靶点。

无量山乌骨鸡肝脏组织发育特征及脂蛋白脂酶基因表达研究

【目的】明确无量山乌骨鸡肝脏组织发育过程中脂质沉积和脂酶活性的变化特征以及与脂蛋白脂酶(lipoprotein lipase,LPL)基因表达的相关性。【方法】以1(D1)、42(D42)、84(D84)、126(D126)日龄共4个阶段的无量山公鸡和母鸡为研究对象,测定体重和肝脏组织重量并计算肝脏指数,HE石蜡切片染色鉴定肝脏组织的形态学变化,采用甘油三酯(triglyceride,TG)检测试剂盒(单试剂GPO-PAP法)检测肝脏组织中TG含量,采用比色法检测LPL和肝酯酶(hepaticlipase,HL)活性,采用实时荧光定量PCR检测肝脏组织中LPL基因mRNA表达量,采用Pearson相关性分析确定LPL基因表达量和肝脏组织各指标之间的相关性。【结果】无量山乌骨鸡公鸡和母鸡在不同生长阶段肝脏重差异均显著(P<0.05),D42和D84肝脏指数分别与D1和D126相比差异显著(P<0.05);公鸡和母鸡肝脏组织中TG含量均在D84时出现峰值;母鸡LPL和HL活性在D126时达到顶峰且显著高于其他阶段(P<0.05),公鸡LPL和HL活性在D42时达到顶峰,公母鸡总脂酶活性分别在D42和D126时达到顶峰且显著高于其他阶段(P<0.05);公鸡和母鸡肝脏组织LPL基因mRNA表达的峰值分别在D42和D1,且母鸡LPL基因mRNA表达量在D1、D42和D126共3个发育阶段均与HL活性呈显著相关(P<0.05)。【结论】无量山乌骨鸡肝脏组织重量、肝脏指数、TG含量、脂酶含量和LPL基因mRNA表达量在不同发育阶段变化较大,而成鸡脂酶活性主要受性别影响,母鸡中LPL基因mRNA表达量与HL活性显著相关。结果为进一步研究无量山乌骨鸡肝脏脂肪代谢调控机制提供科学依据。