Hepatic Lipase Gene Research Articles

Smaller low‐density lipoprotein size as a possible risk factor for the prevalence of coronary artery diseases in haemodialysis patients: Associations of cholesteryl ester transfer protein and the hepatic lipase gene polymorphism with low‐density lipoprotein size

Smaller low-density lipoprotein (LDL) size has recently been reported as a non-traditional lipid risk factor for coronary artery disease (CAD). Cholesteryl ester transfer protein (CETP) and the C/T hepatic lipase (HL) gene polymorphism may promote LDL size reduction via the CETP-mediated exchange of CE for triglyceride (TG) and subsequent HL-mediated TG hydrolysis in LDL. However, little is known about LDL size status and its relationship with CAD prevalence in haemodialysis (HD) patients who are at high risk for atherosclerosis. CETP levels, HL genotypes and LDL size were determined, and the determinants of LDL size and its association with CAD prevalence in HD patients (n = 236) aged over 30 years were investigated. The HD patients had a similar LDL size to the healthy subjects. In the HD group, high-density lipoprotein cholesterol was an independent positive determinant of LDL size, while log(10) (TG) was an independent negative determinant in the high (≥2.1 µg/mL) but not low (<2.1 µg/mL) CETP group. In the patients with hypertriglyceridemia, the high CETP group had a significantly smaller LDL size than the low CETP group. Among the patients with above-median TG levels, the CC genotype and CETP were independent negative determinants of LDL size. In the whole group and the high CETP group, the patients with CAD had a significantly smaller LDL size than those without CAD. Finally, DM and smaller LDL size were identified as independent risk factors for CAD prevalence. These suggest that a smaller LDL size, which is associated with higher levels of TG and CETP and the HL/CC genotype, may serve as a risk factor for CAD in HD patients.

465 ASSOCIATION OF THROMBOMODULIN GENE VARIANTS IN INDIAN PATIENTS WITH CORONARY ARTERY DISEASE (CAD)

Despite a higher prevalence of coronary heart disease risk factors, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than whites. In part, this is thought to be because of the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower triglycerides and higher high-density lipoprotein (HDL) cholesterol. We hypothesized that the −514C>T polymorphism in the hepatic lipase gene (LIPC) plays a significant role in determining a less atherogenic lipoprotein profile observed in men of African origin. Previously conducted studies of the LIPC −514C>T polymorphism in African Americans may have been confounded by a higher level of European admixture; in addition, the results from these studies do not necessarily apply to other African populations because gene-environment interactions may differ. Thus, we compared nuclear magnetic resonance spectroscopy–measured lipoprotein subclass patterns and LIPC −514C>T genotypes in population-based samples of older white American (n = 532) and African American (n = 97) men from the Cardiovascular Health Study to those among older, less admixed, Afro-Caribbean men (n = 205) from the Tobago Health Study. Men of African origin had a more favorable lipoprotein profile than whites. In addition, levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride, and large and small very low-density lipoprotein, small low-density lipoprotein, as well as very low-density lipoprotein particle size, were remarkably lower in Afro-Caribbean men than in either African American or white men. The frequency of the LIPC −514T allele was much higher in Afro-Caribbeans (0.57) and in African Americans (0.49) than in whites (0.20). The −514T allele in both populations of African origin, but not in whites, was associated with elevated large HDL and greater HDL size. Our findings indicate that the higher frequency of the LIPC −514T allele found in men of African origin living in different environments significantly contributes to the more favorable distribution of HDL subclasses compared with whites.

Vertebrate hepatic lipase genes and proteins: a review supported by bioinformatic studies

Hepatic lipase (gene: LIPC; enzyme: HL; E.C.3.1.1.3) is one of three members of the triglyceride lipase family that contributes to vascular lipoprotein degradation and serves a dual role in triglyceride hydrolysis and in facilitating receptor-mediated lipoprotein uptake into the liver. Amino acid sequences, protein structures, and gene locations for vertebrate LIPC (or Lipc for mouse and rat) genes and proteins were sourced from previous reports and vertebrate genome databases. Lipc was distinct from other neutral lipase genes (Lipg encoding endothelial lipase and Lpl encoding lipoprotein lipase [LPL]) and was located on mouse chromosome 9 with nine coding exons on the negative strand. Exon 9 of human LIPC and mouse and rat Lipc genes contained "stop codons" in different positions, causing changes in C-termini length. Vertebrate HL protein subunits shared 58%-97% sequence identities, including active, signal peptide, disulfide bond, and N-glycosylation sites, as well as proprotein convertase ("hinge") and heparin binding regions. Predicted secondary and tertiary structures revealed similarities with the three-dimensional structure reported for horse and human pancreatic lipases. Potential sites for regulating LIPC gene expression included CpG islands near the 5″-untranslated regions of the mouse and rat LIPC genes. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate LIPC gene family with other neutral triglyceride lipase gene families (LIPG and LPL). We conclude that the triglyceride lipase ancestral gene for vertebrate neutral lipase genes (LIPC, LIPG, and LPL) predated the appearance of fish during vertebrate evolution.

Hepatic Lipase, High Density Lipoproteins, and Hypertriglyceridemia

Hepatic lipase (HL) is a lipolytic enzyme that contributes to the regulation of plasma triglyceride (TG) levels. Elevated TG levels may increase the risk of developing coronary heart disease, and studies suggest that mutations in the HL gene may be associated with elevated TG levels and increased risk of coronary heart disease. Hepatic lipase facilitates the clearance of TG from the very low density lipoprotein (VLDL) pool, and this function is governed by the composition and quality of high density lipoprotein (HDL) particles. In humans, HL is a liver resident enzyme regulated by factors that release it from the liver and activate it in the bloodstream. HDL regulates the release of HL from the liver and HDL structure controls HL transport and activation in the circulation. Alterations in HDL-apolipoprotein composition can perturb HL function by inhibiting the release and activation of the enzyme. HDL structure may therefore affect plasma TG levels and coronary heart disease risk.

Cholesteryl ester transfer protein and hepatic lipase gene polymorphisms: Effects on hepatic mRNA levels, plasma lipids and carotid atherosclerosis

ObjectiveHDL modifying effects of cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) depend in part on each other. We studied associations of CETP-Taq1B and -514C>T-LIPC polymorphisms with hepatic mRNA levels, and their combined effects on plasma lipids and carotid atherosclerosis. MethodsWe genotyped the CETP-Taq1B and the -514C>T-LIPC polymorphisms in 67 obese women in whom hepatic CETP and LIPC transcript levels were determined as well as in 1549 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR). Carotid atherosclerosis was assessed by intima-media thickness and extent of plaques (B-score) of the carotid arteries. ResultsIn obese women, CETP-Taq1B and -514C>T-LIPC variant alleles were associated with reduced hepatic levels of CETP and LIPC mRNA, respectively. The CETP and LIPC polymorphisms accounted for 12.9 and 14.4% of the variability in respective transcripts. In the SAPHIR population, CETP-Taq1B showed independent effects on LDL diameter, HDL and LDL cholesterol, apolipoproteins AI and B and cholesterol/HDL cholesterol, while -514C>T-LIPC revealed independent effects on HDL cholesterol and apolipoprotein AI. The two polymorphisms displayed interactions at the level of HDL cholesterol. Compared to subjects carrying wild-type alleles at both loci, subjects homozygous for the CETP wild-type allele, but heterozygous for the LIPC polymorphism and subjects heterozygous for the CETP polymorphism, but homozygous for the LIPC wild-type allele showed an increased risk of carotid atherosclerosis (both P<0.05). ConclusionsCETP and LIPC polymorphisms influence the respective hepatic transcript levels, demonstrate interactions on HDL cholesterol and suggest that imbalances between CETP and LIPC activities may modulate the risk of carotid atherosclerosis.

Relationship of APOA5, PPARγ and HL gene variants with serial changes in childhood body mass index and coronary artery disease risk factors in young adulthood

BackgroundTriglycerides is an independent risk factor for coronary artery disease (CAD) and is especially important in Indians because of high prevalence of hypertriglyceridemia in this population. Both genetic and environmental factors determine triglyceride levels. In a birth cohort from India, hypertriglyceridemia was found in 41% of men and 11% of women. Subjects who had high triglycerides had more rapid body mass index (BMI) or weight gain than rest of the cohort throughout infancy, childhood and adolescence. We analysed polymorphisms in APOA5, hepatic lipase and PPARγ genes and investigated their association with birth weight and serial changes in BMI.ResultsPolymorphisms in APOA5 (-1131T > C, S19W), PPARγ (Pro12Ala) and hepatic lipase (-514C > T) were studied by polymerase chain reaction (PCR) followed by restriction digestion in 1492 subjects from the New Delhi Birth Cohort (NDBC). We assessed whether these polymorphisms influence lipid and other variables and serial changes in BMI, both individually and together.The risk allele of APOA5 (-1131C) resulted in 23.6 mg/dl higher triglycerides as compared to normal allele (P < 0.001). Risk allele of HL (-514T) was associated with significantly higher HDL2 levels (P = 0.002). Except for the marginal association of PPARγ Pro12Ala variation with a lower conditional weight at 6 months, (P = 0.020) and APOA5 S19W with a higher conditional BMI at 11 yrs of age (P = 0.030), none of the other associations between the gene polymorphisms and serial changes in body mass index from birth to young adulthood were significant.ConclusionThe promoter polymorphism in APOA5 was associated with raised serum triglycerides and that of HL with raised HDL2 levels. None of the polymorphisms had any significant relationship with birth weight or serial changes in anthropometry from birth to adulthood in this cohort.

Serum Lipid Biomarkers and Hepatic Lipase Gene Associations with Age-Related Macular Degeneration

A genetic variant in the high-density lipoprotein (HDL) cholesterol pathway, hepatic lipase (LIPC), was discovered to be associated with advanced age-related macular degeneration (AMD) in a genome-wide association study. In this study, we evaluated whether LIPC is associated with serum lipids, and whether this gene and serum lipids are independently associated with AMD. Case-control study. A total of 458 participants from the Progression Study of Macular Degeneration and the Age-Related Eye Disease Ancillary Biomarker Study, including 318 advanced AMD cases with either geographic atrophy (n = 123) or neovascular disease (n = 195) and 140 controls. Participants were genotyped for 8 variants associated with AMD: 2 CFH variants, C2, CFB, C3, CFI, the ARMS2/HTRA1 gene region, and LIPC. Fasting blood specimens were obtained at study onset, and serum levels of total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides were determined. Logistic and linear regression were used to evaluate associations between serum lipids, LIPC genotype, and AMD. LIPC and serum lipid associations with AMD. The minor T allele of the LIPC gene was associated with a reduced risk of AMD (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P = 0.01, trend for number of T alleles, controlling for age and gender). Mean level of HDL was lower (P = 0.05) and mean level of LDL (P = 0.03) was higher in cases of advanced AMD compared with controls. Higher total cholesterol and LDL levels were associated with increased risk of AMD, with P for trend = 0.01 for both, in models controlling for environmental and genetic covariates. The T allele of LIPC was associated with higher levels of HDL, although LIPC was associated with advanced AMD independent of HDL level. The HDL-raising allele of the LIPC gene (T) was associated with a reduced risk of AMD. Higher total cholesterol and LDL levels were associated with increased risk, whereas higher HDL levels tended to reduce the risk of AMD. The specific mechanisms underlying the association between AMD and LIPC require further investigation.

Association between CETP Taq1B and LIPC -514C/T polymorphisms with the serum lipid levels in a group of Tehran's population: a cross sectional study

BackgroundLow level of high density lipoprotein cholesterol (HDL-C) has high prevalence in the Tehran Lipid and Glucose Study (TLGS) cohort. About 50% of the inter-individual variation in serum HDL-C levels is genetically determined. Polymorphisms in cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) genes have been found to be associated with the metabolism and serum concentration of the HDL-C.ObjectivesTo determine the association between Taq1B polymorphism in CETP gene and -514C/T polymorphism in LIPC gene with serum lipid levels and lipid peroxidation in a subgroup of the TLGS population.ResultsSerum HDL-C level had significant association with CETP Taq1B polymorphism and B2B2 subjects had the highest HDL-C levels compared to B2B1 and B1B1 genotypes (37.9 vs. 36.9 and 35.3 mg/dl, respectively; P = 0.01). However, carriers of "B1" allele, in comparison to the non carriers (B2B2), had significantly lower levels of TC (200.1 vs. 215.2 mg/dl; P = 0.005), HDL-C (35.8 vs. 37.9 mg/dl; P = 0.009) and malondialdehyde MDA (4.5 vs. 5.0 nmol/mL; P=0.031). Carriers of the "T" allele in -514C/T polymorphism in LIPC gene had higher means of HDL-C than non carriers (37.7 vs. 35.7 mg/dl, P = 0.04). No other association was found between -514C/T polymorphism and any other serum lipids or MDA level.ConclusionThis study demonstrates the association between Taq1B and -514C/T polymorphisms in the CETP and LIPC genes with the serum HDL-C levels.

Increased Coronary Heart Disease Risk Determined by High High-Density Lipoprotein Cholesterol and C-Reactive Protein: Modulation by Variation in the CETP Gene

Epidemiological evidence strongly favors the notion that the risk of cardiovascular disease (CVD) is inversely related to the plasma high-density lipoprotein (HDL) cholesterol concentration.1 Low HDL cholesterol is still predictive of high CVD risk in subjects with low LDL cholesterol,2 as well as during statin treatment.3 These observational data and other studies, which show that HDL particles contain a large number of antioxidative, antiinflammatory, and antiproliferative proteins, underlie the generally held view that HDL particles have atheroprotective properties.1–5 However, evidence is accumulating supporting the concept that high HDL cholesterol levels do not always predict reduced CVD risk. The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trial and the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk case-control study revealed that (recurrent) CVD risk is not decreased in subjects with the highest HDL cholesterol and the greatest mean HDL particle size.6 More recently, a high HDL cholesterol, high C-reactive protein (CRP) subgroup of individuals at increased risk for a first cardiovascular event was identified in the community-dwelling Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort using the “outcome event mapping approach,” a graphical exploratory data analysis tool that has been originally developed by Corsetti et al.7 Applying this analytic method to the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction cohort, the presence of a subgroup …

Quantitative Assessment of the Effect of Hepatic Lipase Gene Polymorphism on the Risk of Coronary Heart Disease

The human hepatic lipase (LIPC) is a glycoprotein member of the lipase superfamily that has attracted considerable attention as a candidate gene for coronary heart disease (CHD) based on its enzyme function as a key factor in lipoprotein catabolism pathways. In the past decade, a number of case-control studies have been carried out to investigate the relationship between the LIPC polymorphisms and CHD. However, studies on the association between LIPC polymorphisms and CHD remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 11,906 cases and 13,273 controls from 18 published case-control studies was performed. Overall, the summary odds ratio of CHD was 0.87 (95% confidence interval: 0.66-1.15) and 1.03 (95% confidence interval: 0.98-1.07) for LIPC -250A and -514T alleles, respectively. No significant results were observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the stratified analyses according to ethnicity, source of controls, no evidence of any gene-disease association was obtained. Our result suggest that the G-250A, C-514T polymorphisms of LIPC gene are not associated with CHD susceptibility.

Molecular characterization and evolutional analysis of liportein lipase and hepatic lipase gene in Chinese Sturgeon and other six freshwater fishes

In order to study the structural, functional and molecular evolutional relationship of fish liportein lipase (LPL) and hepatic lipase (HL) genes, seven liver LPL and HL cDNA partial sequences were isolated from Acipenser sinensis, Hypophthalmichthys molitrix, Aristichthys nobilis, Ctenopharyngodon idellus, Cirrhinus molitorella, Oreochromis niloticus, Channa maculate by RT-PCR. Three full-length cDNA sequences of LPL, HL of Acipenser sinensis and LPL of Hypophthalmichthys molitrix were obtained by RACEs. From the sequence analysis and homologous results, the amino acid sequences of LPL and HL are relatively conserved in mammals, birds and fishes. Taken together with these obtained amino acid sequences and sequences of all known LPL, HL, EL and PL from other vertebrates, a phylogenetic tree was constructed by neighbor-joining method. The result supports that all of them belong to lipase family.

The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial

BackgroundEpidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD) risk; however, few studies have compared wheat whole grains with wheat refined grains.MethodsThis study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14) and hyperglycemic/hyperinsulinemic (HGI; n = 14) adults. The influence of single-nucleotide polymorphisms, 3 within the APOE gene (E2, E3, E4) and 2 within the hepatic lipase gene promoter (LIPC -514C>T, LIPC -250G>A) were considered.ResultsAt baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glucagon, triacylglycerols (TAG) and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the APOE E3/E3 genotype, LDL-cholesterol (P = 0.02) increased in the NGI group (n = 7), and TAG (P = 0.03) and TAG:HDL-cholesterol (P = 0.04) increased in the HGI group (n = 10), following consumption of whole grain wheat sourdough compared to white bread.ConclusionsIn summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the APOE E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.

Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene ( LIPC )

Advanced age-related macular degeneration (AMD) is the leading cause of late onset blindness. We present results of a genome-wide association study of 979 advanced AMD cases and 1,709 controls using the Affymetrix 6.0 platform with replication in seven additional cohorts (totaling 5,789 unrelated cases and 4,234 unrelated controls). We also present a comprehensive analysis of copy-number variations and polymorphisms for AMD. Our discovery data implicated the association between AMD and a variant in the hepatic lipase gene (LIPC) in the high-density lipoprotein cholesterol (HDL) pathway (discovery P = 4.53e-05 for rs493258). Our LIPC association was strongest for a functional promoter variant, rs10468017, (P = 1.34e-08), that influences LIPC expression and serum HDL levels with a protective effect of the minor T allele (HDL increasing) for advanced wet and dry AMD. The association we found with LIPC was corroborated by the Michigan/Penn/Mayo genome-wide association study; the locus near the tissue inhibitor of metalloproteinase 3 was corroborated by our replication cohort for rs9621532 with P = 3.71e-09. We observed weaker associations with other HDL loci (ABCA1, P = 9.73e-04; cholesterylester transfer protein, P = 1.41e-03; FADS1-3, P = 2.69e-02). Based on a lack of consistent association between HDL increasing alleles and AMD risk, the LIPC association may not be the result of an effect on HDL levels, but it could represent a pleiotropic effect of the same functional component. Results implicate different biologic pathways than previously reported and provide new avenues for prevention and treatment of AMD.

Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase

The farnesoid X receptor (FXR) is a nuclear receptor that regulates gene expression in response to bile acids (BAs). FXR plays an important role in the homeostasis of bile acid, cholesterol, lipoprotein and triglyceride. In this report, we identified fatty acid synthase (FAS) and hepatic lipase (HL) genes as novel target genes of FXR. Human hepatoma HepG2 cells were treated with chenodeoxycholic acid, the natural FXR ligand, and the messenger RNA and protein levels of FAS and HL were determined by RT-PCR and Western blot analysis, respectively. Chenodeoxycholic acid (CDCA) down-regulated the expression of FAS and HL genes in a dose and time-dependent manner in human hepatoma HepG2 cells. In addition, treatment of mice with CDCA significantly decreased the expression of FAS and HL in mouse liver and the activity of HL. These results demonstrated that FAS and HL might be FXR-regulated genes in liver cells. In view of the role of FAS and HL in lipogenesis and plasma lipoprotein metabolism, our results further support the central role of FXR in the homeostasis of fatty acid and lipid.

Association of LIPC -250G&gt;A polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations

BackgroundThe association between -250G>A polymorphism in the promoter region of the hepatic lipase gene (LIPC) and plasma high-density lipoprotein cholesterol (HDL-C) concentration is contradictory in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association of LIPC -250G>A (rs2070895) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.MethodsA total of 778 subjects of Bai Ku Yao and 648 participants of Han Chinese aged 15-80 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LIPC -250G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThe levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequencies of GG, GA and AA genotypes were 50.0%, 43.3% and 6.7% in Bai Ku Yao, and 35.7%, 50.6% and 13.7% in Han (P < 0.01); respectively. The frequencies of G and A alleles were 71.7% and 28.3% in Bai Ku Yao, and 61.0% and 39.0% in Han (P < 0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao were lower in GG genotype than in GA or AA genotype (P < 0.05-0.01). The levels of TC, HDL-C, LDL-C and ApoB in Han were lower in GG genotype than in GA or AA genotype (P < 0.05-0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao, and the levels of HDL-C, LDL-C and ApoB in Han were correlated with genotype and/or allele (P < 0.05 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both ethnic groups.ConclusionsThe differences in the serum lipid profiles between the two ethnic groups might partly result from different genotypic frequency of LIPC -250G>A or different LIPC-enviromental interactions.

Polymorphisms in the hepatic lipase gene affect plasma HDL-cholesterol levels in a Turkish population

We investigated the effects of single nucleotide polymorphisms (SNPs) of the hepatic lipase gene (LIPC) on plasma HDL-cholesterol (HDL-C) levels in Turks, a population with low levels of HDL-C. All exons and six evolutionarily conserved regions from 28 Turkish subjects were sequenced. We found 51 SNPs, nine of which were novel. Those 51 SNPs and SNPs from the National Center for Biotechnology Information dbSNP were evaluated by bioinformatics approaches. The population frequencies and linkage disequilibrium among SNPs from HapMap were combined with results from transcriptional factor prediction tools and the literature to select SNPs for genotyping. We found that five tagging LIPC SNPs, two reported here for the first time, were significantly associated with plasma HDL-C levels in both men and women (n = 2,612). These results were replicated in a separate Turkish cohort (n = 1,164). Plasma HDL-C levels were higher in subjects homozygous for the minor alleles of rs4775041, rs1800588 (-514C>T), and rs11858164 and lower in subjects homozygous for the minor alleles of rs11856322 and rs2242061. These SNPs seemed to have independent and additive effects on plasma HDL-C levels (1.5-5.2 mg/dl). Hepatic lipase activity in a subset (n = 260) of the main cohort was also significantly associated with all five SNPs. Thus, five LIPC SNPs, two novel, are associated with plasma HDL-C levels and hepatic lipase activity in two cohorts of Turkish subjects.

Effects of dietary lipid levels on growth, survival and lipid metabolism during early ontogeny of Pelteobagrus vachelli larvae

A feeding trial was conducted to investigate the effect of dietary lipid level on darkbarbel catfish ( Pelteobagrus vachelli) larvae during ontogeny with regard to growth, survival and lipid utilization. Larvae were fed, from mouth opening to 20 days after hatching (DAH), with five isonitrogenous microdiets containing different lipid levels (58, 74, 111, 151 and 199 g kg − 1 diet). Live prey (newly hatched Artemia, unenriched) was used as the control diet. The activities of lipoprotein lipase (LPL), hepatic lipase (HL), pancreatic lipase (PL) and LPL gene expression at 3 DAH (mouth opening), 6 DAH, 11 DAH and 20 DAH were examined. The results showed that dietary lipid significantly affected survival and growth of darkbarbel catfish larvae. At the end of the feeding trial, larvae fed diets containing 111 to 151 g lipid kg − 1 had significantly higher survival. Specific growth rate (SGR) of larvae fed the diet containing the highest dietary lipid (199 g kg − 1 ) was significantly ( P < 0.05) lower while no significant differences were observed among other groups fed formulated diets. LPL mRNA level generally increased first with increasing dietary lipid levels and then reached a plateau at different sampling ages. A similar pattern was observed for LPL activity only at 6 DAH and 20 DAH. High dietary lipid increased HL activity at 20 DAH. At 6 DAH, highest PL activity was observed at 199 g lipid kg − 1 diet. Higher dietary lipid resulted in earlier elevated activities of LPL, PL and HL. The specific activities of the above three enzymes and LPL mRNA expression were detected at mouth opening and were significantly influenced by age. The activities of these enzymes increased first and then decreased or reached a plateau during development. The results suggest that dietary lipid could modify lipid utilization during ontogeny of darkbarbel catfish larvae.

Activation of hepatic lipase expression by oleic acid: possible involvement of USF1.

Polyunsaturated fatty acids affect gene expression mainly through peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element binding proteins (SREBPs), but how monounsaturated fatty acids affect gene expression is poorly understood. In HepG2 cells, oleate supplementation has been shown to increase secretion of hepatic lipase (HL). We hypothesized that oleate affects HL gene expression at the transcriptional level. To test this, we studied the effect of oleate on HL promoter activity using HepG2 cells and the proximal HL promoter region (700 bp). Oleate increased HL expression and promoter activity 1.3–2.1 fold and reduced SREBP activity by 50%. Downregulation of SREBP activity by incubation with cholesterol+25-hydroxycholesterol had no effect on HL promoter activity. Overexpression of SREBP2, but not SREBP1, reduced HL promoter activity, which was effected mainly through the USF1 binding site at -307/-312. Oleate increased the nuclear abundance of USF1 protein 2.7 ± 0.6 fold, while USF1 levels were reduced by SREBP2 overexpression. We conclude that oleate increases HL gene expression via USF1. USF1 may be an additional fatty acid sensor in liver cells.

Molecular Cloning and Sequence Analysis of Hepatic Lipase Gene in Yak

Li, S., Jiang, M., Liu, Y., Fu, X., Drackley, J.K., Chen, Y., Ye, Y., Wang, Y. and Zhong, J. 2009. Molecular cloning and sequence analysis of hepatic lipase gene in yak. J. Appl. Anim. Res., 36: 97–101. In order to study the biological function of hepatic lipase (hl) gene in yak, the cDNA sequence encoding hepatic lipase from yak was cloned by RT-PCR method using gene specific PCR primers. The cloned cDNA fragment (1540 bp) contained a 1503 bp open reading frame, encoded 500 amino acids (AAs) with a molecular mass of 56.734 kDa. It showed a high level of sequence identity to Bos Taurus (99.40%), Homo sapiens (77.64%), Oryctolagus cuniculus (76.20%), Mus musculus (68.88%), Xenopus laevis (55.27%) and Danio rerio (47.69%). The hl gene was expressed only in liver tissue and not in heart, spleen, kidney and brain tissues. Further analysis of yak HL amino acid sequence implied that it contained a complete lipase active site (VHLIGYSLGA) ranging from 162 to 171 amino acid residues. It also contained two conserved domains, conserved lipase domain (18AAs-350AAs) in its N-terminal and the PLAT domain (353AAs-488AAs) in its C-terminal. The phylogenetic analysis showed that yak and Bos taurus were the closest species. The prediction of secondary structures indicated that HL of yak had the similar secondary structure with other isolated HL. The results of this study suggested that hl gene of yak was similar with Bos taurus and was expressed only in liver tissue.

Association between hepatic lipase −514 C/T promoter polymorphism and myocardial infarction is modified by history of hypercholesterolemia and waist circumference

Background and aims To examine whether the association between the −514 C/T polymorphism of the hepatic lipase gene and myocardial infarction (MI) is modified by history of hypercholesterolemia and increased waist circumference. Methods and results A total of 1940 pairs of nonfatal MI cases and population-based controls were genotyped. Multiple conditional logistic regression was used for data analyses. The −514T variant was not associated with MI in the whole population. However, among people with history of hypercholesterolemia the T allele increased MI risk for heterozygous and homozygous carriers, respectively [OR = 1.25 (95%CI = 0.92–1.70) and OR = 1.59 (95%CI = 1.09–2.32). In contrast, the T allele decreased MI risk among people with no history of hypercholesterolemia [OR = 0.85 (95%CI = 0.70–1.03) and OR = 0.76 (95%CI = 0.60–0.97)], p for interaction = 0.004. Among subjects with normal waist circumference there was no association between the −514T allele and MI for heterozygous and homozygous carriers, respectively [OR = 1.04 (95%CI = 0.86–1.25) and OR = 0.96 (95%CI = 0.77–1.21)], while among subjects with waist circumference above the limits of the metabolic syndrome definition there was a protective association [OR = 0.63 (95%CI = 0.45–0.90) and OR = 0.81 (95%CI = 0.53–1.25) p for interaction = 0.04]. Conclusion The −514 T allele is associated with MI in opposite directions depending on the background of the studied population. This could explain what seem like inconsistent results across studies.