BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor prognosis.However,the mechanism of metastasis remains poorly underst...BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor prognosis.However,the mechanism of metastasis remains poorly understood.AIM To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment.METHODS The candidate molecule lecithin-cholesterol acyltransferase(LCAT)was screened by gene microarray and bioinformatics analysis.The expression levels of LCAT in clinical cohort samples was detected by quantitative realtime polymerase chain reaction and western blotting.The proliferation,migration,invasion and tumor-forming ability were measured by Cell Counting Kit-8,Transwell cell migration,invasion,and clonal formation assays,respectively.Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression.The immunohistochemistry for Ki67,E-cadherin,N-cadherin,matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC.Gene set enrichment analysis(GSEA)on various gene signatures were analyzed with GSEA version 3.0.Three machine-learning algorithms(random forest,support vector machine,and logistic regression)were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases.RESULTS LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues.LCAT was significantly downregulated in HCC tissues,which is correlated with recurrence,metastasis and poor outcome of HCC patients.Functional analysis indicated that LCAT inhibited HCC cell proliferation,migration and invasion both in vitro and in vivo.Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis(HCC size≤3 cm vs 3-9 cm,P<0.001;3-9 cm vs>9 cm,P<0.01;metastatic-free HCC vs extrahepatic metastatic HCC,P<0.05).LCAT suppressed the growth,migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling.Our results indicated that the logistic regression model based on LCAT,TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients.CONCLUSION LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling.LCAT is a prognostic marker and potential therapeutic target for HCC.展开更多
Objective To verify the regulation of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT 2), which is associated with cholesterol metabolism, by saturated fatty acids (SFAs). Methods Palmitic acid (PA), the most abun...Objective To verify the regulation of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT 2), which is associated with cholesterol metabolism, by saturated fatty acids (SFAs). Methods Palmitic acid (PA), the most abundant saturated fatty acid in plasma, and oleic acid (OA), a widely distributed unsaturated fatty acid, were used to treat hepatic cells HepG2, HuH7, and mouse primary hepatocytes. In addition, PA at different concentrations and PA treatment at different durations were applied in HepG2 cells. In in vivo experiment, three-month male C57/BL6 mice were fed with control diet and SFA diet containing hydrogenated coconut oil rich of SFAs. The mRNA level of ACAT2 in those hepatic cells and the mouse livers was detected with real-time polymerase chain reaction (PCR). Results In the three types of hepatic cells treated with PA, that SFA induced significant increase of ACAT2 expression (P<0.01), whereas treatment with OA showed no significant effect. That effect of PA was noticed gradually rising along with the increase of PA concentration and the extension of PA treatment duration (both P<0.05). SFA diet feeding in mice resulted in a short-term and transient increase of ACAT2 expression in vivo, with a peak level appearing in the mice fed with SFA diet for two days (P<0.05). Conclusion SFA may regulate ACAT2 expression in human and mouse hepatic cells and in mouse livers.展开更多
In order to explore the effect and mechanisms of tumor necrosis factor-α （TNF-α） on the activity of the acyl coenzyme A： cholesteryl acyltransferase （ACAT）, THP-I monocytes were cul- tured and induced to differ...In order to explore the effect and mechanisms of tumor necrosis factor-α （TNF-α） on the activity of the acyl coenzyme A： cholesteryl acyltransferase （ACAT）, THP-I monocytes were cul- tured and induced to differentiate into macrophages with phorbol ester. TNF-α （60 ng/mL） was added at different time points into the macrophage-containing medium and the ACAT enzyme activity was measured by quantifying the incorporation of [1-^14C] oleoyl CoA into cholesteryl esters. The expression of ACAT-1 protein and mRNA was respectively detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment with TNF-α （60 ng/mL）. The results indicated that ACAT activity in THP-I macrophages treated with TNF-α was increased in a time-dependent manner. The expression levels of ACAT-1 protein and mRNA were significantly increased in THP-I macrophages after treatment with TNF-α （P〈0.05）. It was suggested that TNF-α could increase the activity of ACAT in THP-1 macrophages by up-regulating the expression of ACAT-1 gene.展开更多
Glycerol-3-phosphate acyltransferase(GPAT) is considered as the rate-limiting enzyme of glycerolipid synthesis pathway and the core element in lysophosphatidic acid(LPA) synthesis. For understanding its catalytic mech...Glycerol-3-phosphate acyltransferase(GPAT) is considered as the rate-limiting enzyme of glycerolipid synthesis pathway and the core element in lysophosphatidic acid(LPA) synthesis. For understanding its catalytic mechanism, the structural biology study is expected, but is always hindered by obtaining crystals for X-ray diffraction analysis. In this study, a progressive strategy to optimize the crystal of microalgae plastidial GPAT was presented. After the expression and purification of GPAT, the crystals were screened by hanging-drop and only clusters were obtained. The crystals were optimized by adjusting temperature, pH, protein concentration, or precipitant, but little improvement. To improve the interaction between protein and precipitant, the isopropanol was applied as co-precipitant. The qualified crystals formed. It's suggested that isopropanol is critical to affect protein crystallization by altering polyethylene glycol(PEG)-water-protein interaction when PEG serves as precipitant. The resulting crystal diffracted to a resolution of 2.75 ? and belonged to space group P1, with unit-cell parameters a = 50.79, b = 80.09, c = 88.21 ?, and α = 62.85, β = 73.04, γ = 80.53?. This work introduced a new strategy to optimize the crystal of the heterogeneous catalysis enzymes like GPAT and provided the fundamental structural information for the oriented synthesis of marine microalgae glycerolipid.展开更多
Triacylglycerols(triglycerides,TAGs)are the major carbon and energy storage forms in various organisms,and important components of cellular membranes and signaling molecules;they have essential functions in multiple p...Triacylglycerols(triglycerides,TAGs)are the major carbon and energy storage forms in various organisms,and important components of cellular membranes and signaling molecules;they have essential functions in multiple physiological processes and stress regulation.Acyl-CoA:diacylglycerol acyltransferase(DGAT)catalyzes the final and only committed acylation step in the synthesis of TAGs in eukaryotes.The present work identified and isolated a novel gene,UpDGAT1,from the green tide alga Ulva prolifera.The activity of UpDGAT1 was confirmed by heterologous expression in a Saccharomyces cerevisiae TAG-deficient quadruple mutant.Results of thin-layer chromatography and BODIPY staining indicated that UpDGAT1 was able to restore TAG synthesis and lipid body formation in the yeast.Lipid analysis of yeast cells revealed that UpDGAT1 showed broad substrate specificity,accepting saturated as well as mono-and polyunsaturated acyl-CoAs as substrates.High salinity and high temperature stresses increased UpDGAT1 expression and TAG accumulation in U.prolifera.The present study provides clues to the functions of UpDGAT1 in TAG accumulation in,and stress adaptation of,U.prolifera.展开更多
Objective To investigate the role of acyl-coenzyme A:cholesterol acyltransferase inhibitor(ACATI) in apoptosis induced by lipids and whether lipids-induced apoptosis is accompanied by increase of free cholesterol in e...Objective To investigate the role of acyl-coenzyme A:cholesterol acyltransferase inhibitor(ACATI) in apoptosis induced by lipids and whether lipids-induced apoptosis is accompanied by increase of free cholesterol in endoplasmic reticulum(ER),in order to further understand the mechanism of lipids-induced apoptosis in advanced atherosclerosis.Methods Human vascular smooth muscle cells(VSMCs) and phorbol 12-myristate 13-acetate(PMA) differentiated THP-1 macrophages were used.Tritiated thymidine incorporation was applied to detect cell proliferation.Cytotoxicity was assessed by lactate dehydrogenase(LDH) release.4',6-diamidino-2-phenylindole(DAPI) staining,caspase-3,-7 assay,and Annexin-V/propidium iodide(PI) staining were used to detect apoptosis.High performance liquid chromatography was used in intracellular free cholesterol and cholesterol ester assay.ER free cholesterol was quantified.Results Different lipids had different effects on proliferation and cytotoxicity of VSMCs.25-hydroxycholesterol(25OHC) had biphasic effects on the proliferation of VSMCs.At low concentration,it stimulated cell proliferation,but turned to proliferation inhibition as concentration reached 15 μg/mL.25OHC and acetylated low density lipoprotein(AcLDL) could respectively induce apoptosis in human VSMCs and PMA differentiated THP-1 macrophages,which was aggravated by ACATI,accompanied by increase of intracellular free cholesterol content.There was also an increase of cholesterol content in ER with AcLDL-induced apoptosis in THP-1 macrophages.Conclusions Lipids could induce apoptosis,accompanied by increase of intracellular free cholesterol content,which could be augmented by ACATI,suggesting that insults resulting in ER free cholesterol rise might be the initiator of apoptosis.展开更多
Horizontal gene transfer(HGT) refers to the flow of genetic materials to non-offspring,and occasionally HGT in plants can improve the adaptation of organisms in new niches due to expanded metabolic capability.Anthocya...Horizontal gene transfer(HGT) refers to the flow of genetic materials to non-offspring,and occasionally HGT in plants can improve the adaptation of organisms in new niches due to expanded metabolic capability.Anthocyanins are an important group of water-soluble red,purple,or blue secondary metabolites,whose diversity results from modification after the main skeleton biosynthesis.Cuscuta is a stem holoparasitic genus,whose members form direct connection with hosts to withdraw water,nutrients,and macromolecules.Such intimate association is thought to increase the frequency of HGT.By transcriptome screening for foreign genes in Cuscuta australis,we discovered that one gene encoding a putative anthocyanin acyltransferase gene of the BAHD family,which is likely to be involved in anthocyanin modification,was acquired by C.australis from Fabaceae through HGT.The anthocyanin acyltransferase-like(AT-like) gene was confirmed to be present in the genome assembly of C.australis and the transcriptomes of Cuscuta pentagona.The higher transcriptional level in old stems is consistent with its putative function in secondary metabolism by stabilizing anthocyanin at neutral pH and thus HGT of this AT-like gene may have improved biotic and abiotic resistance of Cuscuta.展开更多
Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly supp...Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly suppress sebum production and accumulation in sebaceous glands. Objective: We examined the effects of β-cryptoxanthin (β-CRX), which is a carotenoid pigment most abundant in Citrus unshiu Marcovich (Satsuma mandarin orange) and plays a role as a vitamin A precursor on sebum production and accumulation in hamster sebaceous gland cells (sebocytes). Materials and methods: The regulation of sebum production was examined by the measurement of triacylglycerols (TGs), the major sebum component, and oil red O staining in insulindifferentiated hamster sebocytes. The expression of diacylglycerol acyltransferase-1 (DGAT-1), a rate-limiting enzyme of TG biosynthesis, and perilipin 1 (PLIN1), a lipid storage droplet protein, was analyzed using real-time PCR and Western blotting. Results: Hamster sebocytes constitutively produced TGs during cultivation and the production of TGs was enhanced by insulin treatment. Both constitutive and insulin-enhanced TG productions were dose- and time-dependently inhibited by β-CRX as well as 13-cis retinoic acid. In addition, the gene expression of DGAT-1 was suppressed by β-CRX in the sebocytes. Furthermore, the insulin-en- hanced sebum accumulation as lipid droplets was reduced in the β-CRX-treated cells. Moreover, β-CRX was found to suppress the gene expression and production of PLIN1 in insulin-differentiated hamster sebocytes. Conclusions: These results provide novel evidence that β-CRX is an effective candidate for acne therapy by its ability to exert dual inhibitory actions against DGAT-1-dependent TG production and PLIN1-mediated lipiddroplet formation in hamster sebocytes.展开更多
Various lipid metabolism-related factors are essential for Zika virus(ZIKV)replication.In this study,we revealed a crucial role of diacylglycerol O-acyltransferase 2(DGAT2)in ZIKV replication using a short hairpin RNA...Various lipid metabolism-related factors are essential for Zika virus(ZIKV)replication.In this study,we revealed a crucial role of diacylglycerol O-acyltransferase 2(DGAT2)in ZIKV replication using a short hairpin RNA-based gene knockdown technique.The replication of ZIKV was significantly inhibited by DGAT2 depletion in multiple cell lines and restored by trans-complementation with DGAT2.Mechanistically,DGAT2 is recruited in the viral replication complex by interacting with non-structural(NS)proteins.Among them,both human and murine DGAT2s can be cleaved by NS2B3 at the 122R-R-S124 site.Interestingly,the cleavage product of DGAT2 becomes more stable and is sufficient to promote the lipid droplet(LD)formation independent of its enzymatic activity.This work identifies DGAT2 as a novel target of the viral protease NS2B3 and elucidates that DGAT2 is recruited by viral proteins into the replication complex,thereby playing a proviral role by promoting LD formation,which advances our understanding of host–flavivirus interaction.展开更多
The enzymes of the acyl-coenzyme A:cholesterol acyltransferase(ACAT)family are responsible for the in vivo synthesis of neutral lipids.They are potential drug targets for the intervention of atherosclerosis,hyperlipid...The enzymes of the acyl-coenzyme A:cholesterol acyltransferase(ACAT)family are responsible for the in vivo synthesis of neutral lipids.They are potential drug targets for the intervention of atherosclerosis,hyperlipidemia,obesity,type II diabetes and even Alzheimer’s disease.ACAT family enzymes are integral endoplasmic reticulum(ER)membrane proteins and can be divided into ACAT branch and acyl-coenzyme A:diacylglycerol acyltransferase 1(DGAT1)branch according to their substrate specificity.The ACAT branch catalyzes synthesis of cholesteryl esters using long-chain fatty acyl-coenzyme A and cholesterol as substrates,while the DGAT1 branch catalyzes synthesis of triacylglycerols using fatty acylcoenzyme A and diacylglycerol as substrates.In this review,we mainly focus on the recent progress in the structural research of ACAT family enzymes,including their disulfide linkage,membrane topology,subunit interaction and catalysis mechanism.展开更多
Microalgal oils, depending on their degree of unsaturation, can be utilized as either nutritional supplements or fuels; thus, a feedstock with genetically designed and tunable degree of unsaturation is desirable to ma...Microalgal oils, depending on their degree of unsaturation, can be utilized as either nutritional supplements or fuels; thus, a feedstock with genetically designed and tunable degree of unsaturation is desirable to maximize process efficiency and product versatility. Systematic profiling of ex vivo （in yeast）, in vitro, and in vivo activities of type-2 diacylglycerol acyltransferases in Nannochloropsis oceanica （NoDGAT2s or NoDGTTs）, via reverse genetics, revealed that NoDGAT2A prefers saturated fatty acids （SFAs）, NoDGAT2D prefers monounsaturated fatty acids （MUFAs）, and NoDGAT2C exhibits the strongest activity toward polyunsaturated fatty acids （PUFAs）. As NoDGAT2A, 2C, and 2D originated from the green alga, red alga, and eukaryotic host ancestral participants of secondary endosymbiosis, respectively, a mecha- nistic model of oleaginousness was unveiled, in which the indigenous and adopted NoDGAT2s formulated functional complementarity and specific transcript abundance ratio that underlie a rigid SFA：MUFA：PUFA hierarchy in triacylglycerol （TAG）. By rationally modulating the ratio of NoDGAT2A＇：2C^D transcripts, a bank of N. oceanica strains optimized for nutritional supplement or fuel production with a wide range of degree of unsaturation were created, in which proportion of SFAs, MUFAs, and PUFAs in TAG varied by 1.3-, 3.7-, and 11.2-fold, respectively. This established a novel strategy to simultaneously improve productivity and quality of oils from industrial microalgae.展开更多
Brassinosteroids （BRs） play essential roles in regulating various aspects of plant growth and development and in responding to diverse environmental cues, and their metabolism is an important way to regulate their h...Brassinosteroids （BRs） play essential roles in regulating various aspects of plant growth and development and in responding to diverse environmental cues, and their metabolism is an important way to regulate their homeosta-sis in plants. Here, we identified a dominant mutant, dwarf and round leaf-1 （drll-D）, which exhibits weak BR-deficient or BR-insensitive mutant phenotypes, including short and round leaves, prolonged senescence, dwarfed shape, and altered expression levels of the BR-responsive genes. Hypocotyl length and root inhibition assays suggest that the drll-D mutant responds to BRs normally, but has decreased BR signaling outputs. The endogenous levels of several BRs, includ-ing typhasterol （TY）, 6-deoxotyphasterol （6-deoxoTY）, and 6-deoxocastasterone （6-deoxoCS）, are significantly lower in the drll-D mutant than in the wild-type. The DRL1 gene encodes an acyltransferase and is widely expressed in leaves, roots, flowers, and siliques. Plants without DRL1 and its homologs are larger with an enhanced BR signaling. The expres-sion of DRL1 was induced by eBL and inhibited by ABA. DRL1 is involved in the BR metabolism likely by catalyzing the BR conjugation through esterification, which plays important roles in regulating the BR homeostasis and responding to abiotic stresses in Arabidopsis.展开更多
Objective To identify the active compounds from the barks of Betula platyphylla for inhibitory on diacylglycerol acyltransferase（DGAT1）.Methods Bioassay-guided fractionation resulted in the isolation of DGAT1 inhibi...Objective To identify the active compounds from the barks of Betula platyphylla for inhibitory on diacylglycerol acyltransferase（DGAT1）.Methods Bioassay-guided fractionation resulted in the isolation of DGAT1 inhibitory activity of lupane triterpenes.Results Ten compounds were identified as lupenone（1）,lupeol（2）,betulinic acid（3）,betulinaldehyde（4）,betulin（5）,3-deoxybetulonic acid（6）,glochidonol（7）,lup-20/29-ene-1β/3β-diol（8）,3α-hydroxy-lup-20（29）-en-23,28-dioic acid（9）,and 3α,11α-dihydroxy-23-oxo-lup-20（29）-en-28-oic acid（10）.Compounds 3-6,9,and 10 inhibited DGAT1 with IC50 values ranging from（11.2±0.3）to（38.6±1.2）μmol/L.Conclusion Compounds 6,9,and 10 are first isolated from the barks of B.platyphylla.,and compounds 3-6,9,and 10 from the barks of B.platyphylla are responsible for the inhibition on DGAT1.展开更多
Two cDNAs encoding putative type 1 acyl-CoA： diacylglycerol acyltransferases （DGAT1, EC 2.3.1.20）, were cloned from Tetraena mongolica Maxim., an extreme xerophyte with high oil content in the stems. The 1,488-bp a...Two cDNAs encoding putative type 1 acyl-CoA： diacylglycerol acyltransferases （DGAT1, EC 2.3.1.20）, were cloned from Tetraena mongolica Maxim., an extreme xerophyte with high oil content in the stems. The 1,488-bp and 1,485-bp of the open reading frame （ORF） of the two cDNAs, designated as TmDGAT1a and TmDGAT1b, were both predicted to encode proteins of 495 and 494 amino acids, respectively. Southern blot analysis revealed that TmDGAT1a and TmDGAT1b both had low copy numbers in the T. mongolica genome. In addition to ubiquitous expression with different intensity in different tissues, including stems, leaves and roots, TmDGAT1a and TmDGAT1b, were found to be strongly induced by high salinity, drought and osmotic stress, resulting in a remarkable increase of triacylglycerol （TAG） accumulation in T. mongolica plantlets. TmDGAT1a and TmDGAT1b activities were confirmed in the yeast H1246 quadruple mutant （DGA1, LRO1, ARE1, ARE2） by restoring DGAT activity of the mutant host to produce TAG. Overexpression of TmDGAT1a and TmDGAT1b in soybean hairy roots as well as in T. mongolica calli both resulted in an increase in oil content （ranging from 37% to 108%）, accompanied by altered fatty acid profiles.展开更多
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 act...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.展开更多
Diacylglycerol acyltransferase （DGAT） is the key enzyme that catalyzes the triacylglycerol biosynthesis. The comparative analysis was performed on the DGAT1 genes of cotton and other model plants. Sequence analysis ...Diacylglycerol acyltransferase （DGAT） is the key enzyme that catalyzes the triacylglycerol biosynthesis. The comparative analysis was performed on the DGAT1 genes of cotton and other model plants. Sequence analysis showed that most of the DGAT1 genes,with high variation of intron length and high conservation of intron phrase,from the cotton and other model plants had 16 exons. Additionally, 7 conserved motifs were present in these DGAT1 proteins. The core motifs were overlapped with the functional domain of DGAT1 protein. Phylogenetic analysis demonstrated that gene tree was highly consistent to species tree,suggesting that the evolutionary history of species was revealed by gene tree. There was single copy of DGAT1 gene in cotton,but at least two duplicated DGAT1 genes were iden- tified in rice,maize,poplar and moss genomes. The selective pressure analysis showed that the PtDGATla/PtDGATlb was under positive selection,but other four pairs of homologous genes were under negative selection. 17 positively selected sites were identified at subgroup level （P〉0.05）,suggesting these subgroups under relaxed functional constraint. The findings provide a basis for further studying func- tion and evolution of DGAT1 genes in cotton and other model plants.展开更多
AIM： To assess the correlation between the fibrotic area （FA） as calculated by a digital image analysis （DIA）, and to compare the diagnostic accuracy of FibroScan to the other existing Liver fibrosis （LF） marke...AIM： To assess the correlation between the fibrotic area （FA） as calculated by a digital image analysis （DIA）, and to compare the diagnostic accuracy of FibroScan to the other existing Liver fibrosis （LF） markers using the receiver operating curve analysis.METHODS： We recruited 30 patients who underwent a liver resection for three different etiologies including normal liver, hepatitis B, and hepatitis C. Liver stiffness was measured by using a FibroScan. The FA was then calculated by DIA to evaluate LF in order to avoid any sampling bias. RESULTS： The FA negatively correlated with Prothrombin time （PT）, platelet count, lecithin-cholesterol acyltransferase （LCAT）, and pre-albumin （ALB）. On the other hand, the findings of FibroScan correlated with similar markers. The FA positively correlated with FibroScan, serum hyaluronate level, and type Ⅳ collagen level, and aspartate transaminase to platelet ratio index （APRI）. The area under the receiver operating curve for FibroScan was higher than that for the other markers, even though the statistical significance was minimal. CONCLUSION： Our findings suggest that FibroScan can initially be used to assess LF as an alternative to a liver biopsy （LB） and serum diagnosis, because it is a safe method with comparable diagnostic accuracy regarding the existing LF markers.展开更多
Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tentl...Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tently involved in the genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain contain- ing 3 （PNPLA3, also known as adiponutrin）. A nonsyn- onymous single nucleotide polymorphism in PNPLA3 （rs738409 C/G, a coding variant that encodes an amino acid substitution I148M） is significantly associated with fatty liver and histological disease severity, not only in adults but also in children. Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still an open question. A recent article describes new aspects about PNPLA3 gene/protein function and suggests that the I148M variant promotes hepatic lipid synthesis due to a gain of function. We revise here the published data about the role of the I148M variant in lipogen- esis/lipolysis, and suggest putative areas of future research. For instance we explored in silico whether the rs738409 C or G alleles have the ability to modify miRNA binding sites and miRNA gene regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs potentially interacting in the 3＇ UTR region （hsa-miR-769-3p and hsa-miR-516a-3p）. In addition, interesting unanswered questions remain to be explored. For example, PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for insulator activity, and an intronic histone 3 lysine 4 trimethylation peak predicts an enhancer element, cor- roborated by the DNase I hypersensitivity site peak. Finally, an interaction between PNPLA3 and glycerol- 3-phosphate acyltransferase 2 is suggested by data miming.展开更多
AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. ...AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.展开更多
基金Supported by the National Natural Science Foundation of China,No.92159305National Key R&D Program of China,No.2023YFC2308104.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor prognosis.However,the mechanism of metastasis remains poorly understood.AIM To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment.METHODS The candidate molecule lecithin-cholesterol acyltransferase(LCAT)was screened by gene microarray and bioinformatics analysis.The expression levels of LCAT in clinical cohort samples was detected by quantitative realtime polymerase chain reaction and western blotting.The proliferation,migration,invasion and tumor-forming ability were measured by Cell Counting Kit-8,Transwell cell migration,invasion,and clonal formation assays,respectively.Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression.The immunohistochemistry for Ki67,E-cadherin,N-cadherin,matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC.Gene set enrichment analysis(GSEA)on various gene signatures were analyzed with GSEA version 3.0.Three machine-learning algorithms(random forest,support vector machine,and logistic regression)were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases.RESULTS LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues.LCAT was significantly downregulated in HCC tissues,which is correlated with recurrence,metastasis and poor outcome of HCC patients.Functional analysis indicated that LCAT inhibited HCC cell proliferation,migration and invasion both in vitro and in vivo.Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis(HCC size≤3 cm vs 3-9 cm,P<0.001;3-9 cm vs>9 cm,P<0.01;metastatic-free HCC vs extrahepatic metastatic HCC,P<0.05).LCAT suppressed the growth,migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling.Our results indicated that the logistic regression model based on LCAT,TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients.CONCLUSION LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling.LCAT is a prognostic marker and potential therapeutic target for HCC.
基金Supported by National Natural Science Foundation of China (30721063)National High Technology Research and Development Program of China (863 Program) (2006AA02A406)+1 种基金National Basic Research Program of China (973 Program) (2006CB503801)Special Fund of the National Laboratory of China (2060204)
文摘Objective To verify the regulation of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT 2), which is associated with cholesterol metabolism, by saturated fatty acids (SFAs). Methods Palmitic acid (PA), the most abundant saturated fatty acid in plasma, and oleic acid (OA), a widely distributed unsaturated fatty acid, were used to treat hepatic cells HepG2, HuH7, and mouse primary hepatocytes. In addition, PA at different concentrations and PA treatment at different durations were applied in HepG2 cells. In in vivo experiment, three-month male C57/BL6 mice were fed with control diet and SFA diet containing hydrogenated coconut oil rich of SFAs. The mRNA level of ACAT2 in those hepatic cells and the mouse livers was detected with real-time polymerase chain reaction (PCR). Results In the three types of hepatic cells treated with PA, that SFA induced significant increase of ACAT2 expression (P<0.01), whereas treatment with OA showed no significant effect. That effect of PA was noticed gradually rising along with the increase of PA concentration and the extension of PA treatment duration (both P<0.05). SFA diet feeding in mice resulted in a short-term and transient increase of ACAT2 expression in vivo, with a peak level appearing in the mice fed with SFA diet for two days (P<0.05). Conclusion SFA may regulate ACAT2 expression in human and mouse hepatic cells and in mouse livers.
基金This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30170378)
文摘In order to explore the effect and mechanisms of tumor necrosis factor-α （TNF-α） on the activity of the acyl coenzyme A： cholesteryl acyltransferase （ACAT）, THP-I monocytes were cul- tured and induced to differentiate into macrophages with phorbol ester. TNF-α （60 ng/mL） was added at different time points into the macrophage-containing medium and the ACAT enzyme activity was measured by quantifying the incorporation of [1-^14C] oleoyl CoA into cholesteryl esters. The expression of ACAT-1 protein and mRNA was respectively detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment with TNF-α （60 ng/mL）. The results indicated that ACAT activity in THP-I macrophages treated with TNF-α was increased in a time-dependent manner. The expression levels of ACAT-1 protein and mRNA were significantly increased in THP-I macrophages after treatment with TNF-α （P〈0.05）. It was suggested that TNF-α could increase the activity of ACAT in THP-1 macrophages by up-regulating the expression of ACAT-1 gene.
基金financially supported by the National Natural Science Foundation of China (Nos. 21576253, 31500294 and 31470432)
文摘Glycerol-3-phosphate acyltransferase(GPAT) is considered as the rate-limiting enzyme of glycerolipid synthesis pathway and the core element in lysophosphatidic acid(LPA) synthesis. For understanding its catalytic mechanism, the structural biology study is expected, but is always hindered by obtaining crystals for X-ray diffraction analysis. In this study, a progressive strategy to optimize the crystal of microalgae plastidial GPAT was presented. After the expression and purification of GPAT, the crystals were screened by hanging-drop and only clusters were obtained. The crystals were optimized by adjusting temperature, pH, protein concentration, or precipitant, but little improvement. To improve the interaction between protein and precipitant, the isopropanol was applied as co-precipitant. The qualified crystals formed. It's suggested that isopropanol is critical to affect protein crystallization by altering polyethylene glycol(PEG)-water-protein interaction when PEG serves as precipitant. The resulting crystal diffracted to a resolution of 2.75 ? and belonged to space group P1, with unit-cell parameters a = 50.79, b = 80.09, c = 88.21 ?, and α = 62.85, β = 73.04, γ = 80.53?. This work introduced a new strategy to optimize the crystal of the heterogeneous catalysis enzymes like GPAT and provided the fundamental structural information for the oriented synthesis of marine microalgae glycerolipid.
基金Foundation item:The National Key Research and Development Program of China under contract No.2016YFC1402102the Central Public-interest Scientific Institution Basal Research Fund,CAFS under contract Nos 2020TD19 and 2020TD27+4 种基金the Major Scientific and Technological Innovation Project of Shandong Provincial Key Research and Development Program under contract 2019JZZY020706the International Exchange and Cooperation in Agriculture,Ministry of Agriculture and Rural Affairs of China-Science,Technology and Innovation Cooperation in Aquaculture with Tropical Countries along the Belt and RoadChina Agriculture Research System under contract No.CARS-50the Taishan Scholars Funding and Talent Projects of Distinguished Scientific Scholars in Agriculturethe National Ten Thousand Youth Talents Plan of 2014 under contract No.W02070268.
文摘Triacylglycerols(triglycerides,TAGs)are the major carbon and energy storage forms in various organisms,and important components of cellular membranes and signaling molecules;they have essential functions in multiple physiological processes and stress regulation.Acyl-CoA:diacylglycerol acyltransferase(DGAT)catalyzes the final and only committed acylation step in the synthesis of TAGs in eukaryotes.The present work identified and isolated a novel gene,UpDGAT1,from the green tide alga Ulva prolifera.The activity of UpDGAT1 was confirmed by heterologous expression in a Saccharomyces cerevisiae TAG-deficient quadruple mutant.Results of thin-layer chromatography and BODIPY staining indicated that UpDGAT1 was able to restore TAG synthesis and lipid body formation in the yeast.Lipid analysis of yeast cells revealed that UpDGAT1 showed broad substrate specificity,accepting saturated as well as mono-and polyunsaturated acyl-CoAs as substrates.High salinity and high temperature stresses increased UpDGAT1 expression and TAG accumulation in U.prolifera.The present study provides clues to the functions of UpDGAT1 in TAG accumulation in,and stress adaptation of,U.prolifera.
基金Supported by National Natural Science Foundation of China (30700373)
文摘Objective To investigate the role of acyl-coenzyme A:cholesterol acyltransferase inhibitor(ACATI) in apoptosis induced by lipids and whether lipids-induced apoptosis is accompanied by increase of free cholesterol in endoplasmic reticulum(ER),in order to further understand the mechanism of lipids-induced apoptosis in advanced atherosclerosis.Methods Human vascular smooth muscle cells(VSMCs) and phorbol 12-myristate 13-acetate(PMA) differentiated THP-1 macrophages were used.Tritiated thymidine incorporation was applied to detect cell proliferation.Cytotoxicity was assessed by lactate dehydrogenase(LDH) release.4',6-diamidino-2-phenylindole(DAPI) staining,caspase-3,-7 assay,and Annexin-V/propidium iodide(PI) staining were used to detect apoptosis.High performance liquid chromatography was used in intracellular free cholesterol and cholesterol ester assay.ER free cholesterol was quantified.Results Different lipids had different effects on proliferation and cytotoxicity of VSMCs.25-hydroxycholesterol(25OHC) had biphasic effects on the proliferation of VSMCs.At low concentration,it stimulated cell proliferation,but turned to proliferation inhibition as concentration reached 15 μg/mL.25OHC and acetylated low density lipoprotein(AcLDL) could respectively induce apoptosis in human VSMCs and PMA differentiated THP-1 macrophages,which was aggravated by ACATI,accompanied by increase of intracellular free cholesterol content.There was also an increase of cholesterol content in ER with AcLDL-induced apoptosis in THP-1 macrophages.Conclusions Lipids could induce apoptosis,accompanied by increase of intracellular free cholesterol content,which could be augmented by ACATI,suggesting that insults resulting in ER free cholesterol rise might be the initiator of apoptosis.
基金Acknowledgments This work was supported by the National Natural Science Foundation of China （No. 31301037 and 31470012 to G.S.）, the Natural Science Foundation of Yunnan Province of China （No. 2013FB068 to G.S.）, the Young Academic and Technical Leader Raising Foundation of Yunnan Province （No. 2014HB046, to G.S.）, the Western Light Talent Culture Project of the Chinese Academy of Sciences （to G.S.）, and the Yunnan Recruitment Program of Experts in Sciences （2012HA016 to J.W.）.
文摘Horizontal gene transfer(HGT) refers to the flow of genetic materials to non-offspring,and occasionally HGT in plants can improve the adaptation of organisms in new niches due to expanded metabolic capability.Anthocyanins are an important group of water-soluble red,purple,or blue secondary metabolites,whose diversity results from modification after the main skeleton biosynthesis.Cuscuta is a stem holoparasitic genus,whose members form direct connection with hosts to withdraw water,nutrients,and macromolecules.Such intimate association is thought to increase the frequency of HGT.By transcriptome screening for foreign genes in Cuscuta australis,we discovered that one gene encoding a putative anthocyanin acyltransferase gene of the BAHD family,which is likely to be involved in anthocyanin modification,was acquired by C.australis from Fabaceae through HGT.The anthocyanin acyltransferase-like(AT-like) gene was confirmed to be present in the genome assembly of C.australis and the transcriptomes of Cuscuta pentagona.The higher transcriptional level in old stems is consistent with its putative function in secondary metabolism by stabilizing anthocyanin at neutral pH and thus HGT of this AT-like gene may have improved biotic and abiotic resistance of Cuscuta.
文摘Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly suppress sebum production and accumulation in sebaceous glands. Objective: We examined the effects of β-cryptoxanthin (β-CRX), which is a carotenoid pigment most abundant in Citrus unshiu Marcovich (Satsuma mandarin orange) and plays a role as a vitamin A precursor on sebum production and accumulation in hamster sebaceous gland cells (sebocytes). Materials and methods: The regulation of sebum production was examined by the measurement of triacylglycerols (TGs), the major sebum component, and oil red O staining in insulindifferentiated hamster sebocytes. The expression of diacylglycerol acyltransferase-1 (DGAT-1), a rate-limiting enzyme of TG biosynthesis, and perilipin 1 (PLIN1), a lipid storage droplet protein, was analyzed using real-time PCR and Western blotting. Results: Hamster sebocytes constitutively produced TGs during cultivation and the production of TGs was enhanced by insulin treatment. Both constitutive and insulin-enhanced TG productions were dose- and time-dependently inhibited by β-CRX as well as 13-cis retinoic acid. In addition, the gene expression of DGAT-1 was suppressed by β-CRX in the sebocytes. Furthermore, the insulin-en- hanced sebum accumulation as lipid droplets was reduced in the β-CRX-treated cells. Moreover, β-CRX was found to suppress the gene expression and production of PLIN1 in insulin-differentiated hamster sebocytes. Conclusions: These results provide novel evidence that β-CRX is an effective candidate for acne therapy by its ability to exert dual inhibitory actions against DGAT-1-dependent TG production and PLIN1-mediated lipiddroplet formation in hamster sebocytes.
基金supported by the National Natural Science Foundation of China(82471389,92169110,and 82271385)Natural Science Foundation of Guangdong Province(2022A1515010451,2024A1515010471,and 2023A1515010476)Guangzhou Municipal Science and Technology Program(202206010114 and 2023A04J2235).
文摘Various lipid metabolism-related factors are essential for Zika virus(ZIKV)replication.In this study,we revealed a crucial role of diacylglycerol O-acyltransferase 2(DGAT2)in ZIKV replication using a short hairpin RNA-based gene knockdown technique.The replication of ZIKV was significantly inhibited by DGAT2 depletion in multiple cell lines and restored by trans-complementation with DGAT2.Mechanistically,DGAT2 is recruited in the viral replication complex by interacting with non-structural(NS)proteins.Among them,both human and murine DGAT2s can be cleaved by NS2B3 at the 122R-R-S124 site.Interestingly,the cleavage product of DGAT2 becomes more stable and is sufficient to promote the lipid droplet(LD)formation independent of its enzymatic activity.This work identifies DGAT2 as a novel target of the viral protease NS2B3 and elucidates that DGAT2 is recruited by viral proteins into the replication complex,thereby playing a proviral role by promoting LD formation,which advances our understanding of host–flavivirus interaction.
文摘The enzymes of the acyl-coenzyme A:cholesterol acyltransferase(ACAT)family are responsible for the in vivo synthesis of neutral lipids.They are potential drug targets for the intervention of atherosclerosis,hyperlipidemia,obesity,type II diabetes and even Alzheimer’s disease.ACAT family enzymes are integral endoplasmic reticulum(ER)membrane proteins and can be divided into ACAT branch and acyl-coenzyme A:diacylglycerol acyltransferase 1(DGAT1)branch according to their substrate specificity.The ACAT branch catalyzes synthesis of cholesteryl esters using long-chain fatty acyl-coenzyme A and cholesterol as substrates,while the DGAT1 branch catalyzes synthesis of triacylglycerols using fatty acylcoenzyme A and diacylglycerol as substrates.In this review,we mainly focus on the recent progress in the structural research of ACAT family enzymes,including their disulfide linkage,membrane topology,subunit interaction and catalysis mechanism.
文摘Microalgal oils, depending on their degree of unsaturation, can be utilized as either nutritional supplements or fuels; thus, a feedstock with genetically designed and tunable degree of unsaturation is desirable to maximize process efficiency and product versatility. Systematic profiling of ex vivo （in yeast）, in vitro, and in vivo activities of type-2 diacylglycerol acyltransferases in Nannochloropsis oceanica （NoDGAT2s or NoDGTTs）, via reverse genetics, revealed that NoDGAT2A prefers saturated fatty acids （SFAs）, NoDGAT2D prefers monounsaturated fatty acids （MUFAs）, and NoDGAT2C exhibits the strongest activity toward polyunsaturated fatty acids （PUFAs）. As NoDGAT2A, 2C, and 2D originated from the green alga, red alga, and eukaryotic host ancestral participants of secondary endosymbiosis, respectively, a mecha- nistic model of oleaginousness was unveiled, in which the indigenous and adopted NoDGAT2s formulated functional complementarity and specific transcript abundance ratio that underlie a rigid SFA：MUFA：PUFA hierarchy in triacylglycerol （TAG）. By rationally modulating the ratio of NoDGAT2A＇：2C^D transcripts, a bank of N. oceanica strains optimized for nutritional supplement or fuel production with a wide range of degree of unsaturation were created, in which proportion of SFAs, MUFAs, and PUFAs in TAG varied by 1.3-, 3.7-, and 11.2-fold, respectively. This established a novel strategy to simultaneously improve productivity and quality of oils from industrial microalgae.
文摘Brassinosteroids （BRs） play essential roles in regulating various aspects of plant growth and development and in responding to diverse environmental cues, and their metabolism is an important way to regulate their homeosta-sis in plants. Here, we identified a dominant mutant, dwarf and round leaf-1 （drll-D）, which exhibits weak BR-deficient or BR-insensitive mutant phenotypes, including short and round leaves, prolonged senescence, dwarfed shape, and altered expression levels of the BR-responsive genes. Hypocotyl length and root inhibition assays suggest that the drll-D mutant responds to BRs normally, but has decreased BR signaling outputs. The endogenous levels of several BRs, includ-ing typhasterol （TY）, 6-deoxotyphasterol （6-deoxoTY）, and 6-deoxocastasterone （6-deoxoCS）, are significantly lower in the drll-D mutant than in the wild-type. The DRL1 gene encodes an acyltransferase and is widely expressed in leaves, roots, flowers, and siliques. Plants without DRL1 and its homologs are larger with an enhanced BR signaling. The expres-sion of DRL1 was induced by eBL and inhibited by ABA. DRL1 is involved in the BR metabolism likely by catalyzing the BR conjugation through esterification, which plays important roles in regulating the BR homeostasis and responding to abiotic stresses in Arabidopsis.
基金Science and Technology Development Program of Jilin Province(201205099)
文摘Objective To identify the active compounds from the barks of Betula platyphylla for inhibitory on diacylglycerol acyltransferase（DGAT1）.Methods Bioassay-guided fractionation resulted in the isolation of DGAT1 inhibitory activity of lupane triterpenes.Results Ten compounds were identified as lupenone（1）,lupeol（2）,betulinic acid（3）,betulinaldehyde（4）,betulin（5）,3-deoxybetulonic acid（6）,glochidonol（7）,lup-20/29-ene-1β/3β-diol（8）,3α-hydroxy-lup-20（29）-en-23,28-dioic acid（9）,and 3α,11α-dihydroxy-23-oxo-lup-20（29）-en-28-oic acid（10）.Compounds 3-6,9,and 10 inhibited DGAT1 with IC50 values ranging from（11.2±0.3）to（38.6±1.2）μmol/L.Conclusion Compounds 6,9,and 10 are first isolated from the barks of B.platyphylla.,and compounds 3-6,9,and 10 from the barks of B.platyphylla are responsible for the inhibition on DGAT1.
基金supported by the National Natural Science Foundation of China (30770224)the National Basic Research Program of China (2011CBA00901)
文摘Two cDNAs encoding putative type 1 acyl-CoA： diacylglycerol acyltransferases （DGAT1, EC 2.3.1.20）, were cloned from Tetraena mongolica Maxim., an extreme xerophyte with high oil content in the stems. The 1,488-bp and 1,485-bp of the open reading frame （ORF） of the two cDNAs, designated as TmDGAT1a and TmDGAT1b, were both predicted to encode proteins of 495 and 494 amino acids, respectively. Southern blot analysis revealed that TmDGAT1a and TmDGAT1b both had low copy numbers in the T. mongolica genome. In addition to ubiquitous expression with different intensity in different tissues, including stems, leaves and roots, TmDGAT1a and TmDGAT1b, were found to be strongly induced by high salinity, drought and osmotic stress, resulting in a remarkable increase of triacylglycerol （TAG） accumulation in T. mongolica plantlets. TmDGAT1a and TmDGAT1b activities were confirmed in the yeast H1246 quadruple mutant （DGA1, LRO1, ARE1, ARE2） by restoring DGAT activity of the mutant host to produce TAG. Overexpression of TmDGAT1a and TmDGAT1b in soybean hairy roots as well as in T. mongolica calli both resulted in an increase in oil content （ranging from 37% to 108%）, accompanied by altered fatty acid profiles.
文摘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.
基金Supported by Youth Science Research Fund of Zhoukou Normal University in 2005(zknu B315213)
文摘Diacylglycerol acyltransferase （DGAT） is the key enzyme that catalyzes the triacylglycerol biosynthesis. The comparative analysis was performed on the DGAT1 genes of cotton and other model plants. Sequence analysis showed that most of the DGAT1 genes,with high variation of intron length and high conservation of intron phrase,from the cotton and other model plants had 16 exons. Additionally, 7 conserved motifs were present in these DGAT1 proteins. The core motifs were overlapped with the functional domain of DGAT1 protein. Phylogenetic analysis demonstrated that gene tree was highly consistent to species tree,suggesting that the evolutionary history of species was revealed by gene tree. There was single copy of DGAT1 gene in cotton,but at least two duplicated DGAT1 genes were iden- tified in rice,maize,poplar and moss genomes. The selective pressure analysis showed that the PtDGATla/PtDGATlb was under positive selection,but other four pairs of homologous genes were under negative selection. 17 positively selected sites were identified at subgroup level （P〉0.05）,suggesting these subgroups under relaxed functional constraint. The findings provide a basis for further studying func- tion and evolution of DGAT1 genes in cotton and other model plants.
基金Supported by the Grants-in-Aid from the Society for the Promotion of Science, Sapporo Medical University for T. Mizuguchi, and Grants-in-Aid from the Ministry of Education, Culture, Sports Science and Technology, Japan. No. 18591519 for T. Mizuguchi, No. 17591420 for T. Katsuramaki, and No. 15390403 for K. Hirata
文摘AIM： To assess the correlation between the fibrotic area （FA） as calculated by a digital image analysis （DIA）, and to compare the diagnostic accuracy of FibroScan to the other existing Liver fibrosis （LF） markers using the receiver operating curve analysis.METHODS： We recruited 30 patients who underwent a liver resection for three different etiologies including normal liver, hepatitis B, and hepatitis C. Liver stiffness was measured by using a FibroScan. The FA was then calculated by DIA to evaluate LF in order to avoid any sampling bias. RESULTS： The FA negatively correlated with Prothrombin time （PT）, platelet count, lecithin-cholesterol acyltransferase （LCAT）, and pre-albumin （ALB）. On the other hand, the findings of FibroScan correlated with similar markers. The FA positively correlated with FibroScan, serum hyaluronate level, and type Ⅳ collagen level, and aspartate transaminase to platelet ratio index （APRI）. The area under the receiver operating curve for FibroScan was higher than that for the other markers, even though the statistical significance was minimal. CONCLUSION： Our findings suggest that FibroScan can initially be used to assess LF as an alternative to a liver biopsy （LB） and serum diagnosis, because it is a safe method with comparable diagnostic accuracy regarding the existing LF markers.
基金Supported by Grants PICT 2008-1521 and PICT 2010 0441,from National Agency for Science and TechnologyUBACYT CM04,from Universidad de Buenos AiresSookoian S and Pirola CJ belong to National Council of Scientific and Technical Research
文摘Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tently involved in the genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain contain- ing 3 （PNPLA3, also known as adiponutrin）. A nonsyn- onymous single nucleotide polymorphism in PNPLA3 （rs738409 C/G, a coding variant that encodes an amino acid substitution I148M） is significantly associated with fatty liver and histological disease severity, not only in adults but also in children. Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still an open question. A recent article describes new aspects about PNPLA3 gene/protein function and suggests that the I148M variant promotes hepatic lipid synthesis due to a gain of function. We revise here the published data about the role of the I148M variant in lipogen- esis/lipolysis, and suggest putative areas of future research. For instance we explored in silico whether the rs738409 C or G alleles have the ability to modify miRNA binding sites and miRNA gene regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs potentially interacting in the 3＇ UTR region （hsa-miR-769-3p and hsa-miR-516a-3p）. In addition, interesting unanswered questions remain to be explored. For example, PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for insulator activity, and an intronic histone 3 lysine 4 trimethylation peak predicts an enhancer element, cor- roborated by the DNase I hypersensitivity site peak. Finally, an interaction between PNPLA3 and glycerol- 3-phosphate acyltransferase 2 is suggested by data miming.
基金Supported by the Grants From Ligue Nationale Contre le Cancer,Comités Départementaux de la Manche,de l'Orne et du Calvados and from Université de Metz
文摘AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.
