Search results for "TM6SF2"

showing 7 items of 17 documents

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

2020

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. Approach and Results: We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor (FGF) 19 levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain containing 3 (PNPLA3), and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and nonlean NAFLD were investigated in a cohort of Caucasian patients with biopsy-proven NAFLD (n …

Male0301 basic medicineReceptors Cytoplasmic and NuclearGut floraMice0302 clinical medicineNon-alcoholic Fatty Liver DiseaseFibrosisNonalcoholic fatty liver diseasebiologyMiddle AgedNAFLD; bile acids; fibrosis; gut microbiota; leanPhospholipases A2 Calcium-IndependentFemale030211 gastroenterology & hepatologyfibrosiAdultmedicine.medical_specialtydigestive systemBile Acids and SaltsCyclic N-Oxides03 medical and health sciencesThinnessInternal medicineNAFLDmedicinebile acidAnimalsHumansbile acidsHepatologygut microbiotabusiness.industryFGF15fibrosisnutritional and metabolic diseasesFGF19leanmedicine.diseasebiology.organism_classificationNAFLD fibrosis lean bile acids gut microbiotadigestive system diseasesGastrointestinal MicrobiomeFibroblast Growth FactorsMice Inbred C57BLDisease Models Animal030104 developmental biologyEndocrinologyFarnesoid X receptorSteatohepatitisbusinessTropanesTM6SF2
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Risk of chemotherapy-associated liver injury (CALI) in PNPLA3 p.148M allele carriers: Preliminary results of a transient elastography-based study

2019

Liver steatosis is one of the side effects of chemotherapy. The PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 p.G17E variants represent genetic determinants for progressive liver diseases. Here, we investigate their association with chemotherapy-associated steatosis.Prospectively, we recruited 87 patients undergoing systemic chemotherapy for gastrointestinal cancers. Hepatic fat (controlled attenuation parameter, CAP) and liver stiffness (LSM) were measured non-invasively before the initiation of chemotherapy (T0) and after at least two (T1) and four cycles (T2). Genetic variants were genotyped using allelic discrimination assays.In the final dataset (n = 60) patients demonstrated the following…

MaleHeterozygotemedicine.medical_specialtymedicine.medical_treatmentAntineoplastic AgentsGastroenterology03 medical and health sciences0302 clinical medicineFat accumulationInternal medicinemedicineHumansGenetic Predisposition to DiseaseAdiponutrinProspective StudiesAlleleeducationAllelesTriglyceridesAgedLiver injuryChemotherapyeducation.field_of_studyPolymorphism GeneticHepatologybusiness.industryGastroenterologyMembrane ProteinsLipaseMiddle Agedmedicine.diseaseFatty LiverLiver030220 oncology & carcinogenesisElasticity Imaging TechniquesFemale030211 gastroenterology & hepatologySteatosisTransient elastographybusinessAcyltransferasesTM6SF2Digestive and Liver Disease
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Identification of molecular pathophysiological mechanisms of non-alcoholic fatty liver disease (NAFLD)

2018

Alkohola neizraisītā taukaino aknu slimība (NATAS) ietver plaša spektra izmaiņas aknās: no pārmērīgas tauku uzkrāšanās līdz pat cirozei. NATAS ģenētiskās komponentes noteikšanai tika veikta visa genoma asociāciju pētījumus (GWAS). Polimorfismi Pnpla3 (I148M; rs738409) un Tm6sf2 (E167K; rs58542926) gēnos ir asociēti ar paaugstinātu lipīdu uzkrāšanos aknās. PNPLA3 I148M varianta proteīns pastiprināti uzkrājas uz šūnu tauku lodīšu virsmas, kas traucē tauku lodīšu normālu funkciju. Proteīna TM6SF2 167K variants izraisa proteīna nestabilitāti un ātrāku tā degradāciju. Tālākie pētījumi parāda, ka TM6SF2 ir saistīts ar aknu ļoti zema blīvuma lipoproteīnu (VLDL) veidošanu vai ekskrēciju. Izpratne p…

NATASInternal MedicineMedicinePNPLA3TM6SF2Medicīna
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The burden of hepatocellular carcinoma in non-alcoholic fatty liver disease: Screening issue and future perspectives

2019

In recent decades, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the Western world, and the occurrence of its complications, such as hepatocellular carcinoma (HCC), has rapidly increased. Obesity and diabetes are considered not only the main triggers for the development of the disease, but also two independent risk factors for HCC. Single nucleotide polymorphisms (such as PNPLA3, TM6SF2 and MBOAT7) are related to the susceptibility to the development of HCC and its progression. Therefore, an appropriate follow-up of these patients is needed for the early diagnosis and treatment of HCC. To date, international guidelines recommend the use of ultrasonogr…

OncologyHepatocellular carcinomaDiseaseReviewlcsh:ChemistryLiver disease0302 clinical medicineDisease ScreeningRisk FactorsMass ScreeningHCClcsh:QH301-705.5SpectroscopyFatty liverLiver NeoplasmsGeneral MedicineComputer Science Applications030220 oncology & carcinogenesisHepatocellular carcinoma030211 gastroenterology & hepatologyMiRNAmedicine.medical_specialtyMicro RNACarcinoma HepatocellularSingle-nucleotide polymorphismCatalysisTM6SF2Inorganic ChemistryDiabetes Complications03 medical and health sciencesDiabetes mellitusInternal medicineNAFLDmedicineAnimalsHumansObesityPhysical and Theoretical ChemistryMolecular BiologyPNPLA3Long non-conding RNAbusiness.industryOrganic Chemistrymedicine.diseasedigestive system diseasesLncRNAlcsh:Biology (General)lcsh:QD1-999businessTM6SF2Non-alcoholic fatty liver disease
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Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.

2020

Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…

Research paperTGFβ Transforming Growth Factor BetaIntracellular SpaceCRISPR Clustered Regularly Interspaced Short Palindromic RepeatshHEPS Human HepatocytesMice0302 clinical medicineLPIAT1DAG Diacylglyceroli.p. Intraperitonealmedia_commonFatty AcidsGeneral Medicine3. Good health030220 oncology & carcinogenesisHOMA-IR homeostasis Model Assessment of Insulin ResistanceMPO morpholinolcsh:Medicine (General)medicine.medical_specialtyPE Phosphatidyl-EthanolamineNashGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesTNFα tumor Necrosis Factor AlphaLDL Low Density LipoproteinsHyperinsulinismNAFLDSD Standard Dietmedia_common.cataloged_instanceHumansCPT1 Carnitine Palmitoyltransferase IPhosphatidylinositolGene SilencingEuropean unionVLDL Very Low Density Lipoproteinlcsh:RhHSC Human Hepatic Stellate Cellsmedicine.diseaseLipid MetabolismOA Oleic AcidCI Confidence IntervalMboat7 Membrane bound O-acyltransferase domain containing 7MCD methionine choline deficient diet030104 developmental biologyEndocrinologychemistryCDP Cytidine-DiphosphateFOXO1 Forkhead Box protein O1NAFLD nonalcoholic fatty liver diseaseSteatohepatitisBMI Body Mass IndexCL CardiolipinAcyltransferases0301 basic medicineAlcoholic liver diseaseCXCL10 C-X-C Motif Chemokine 10lcsh:Medicinechemistry.chemical_compoundNon-alcoholic Fatty Liver DiseaseIFG Impaired Fasting GlucoseAPOB Apolipoprotein BNonalcoholic fatty liver diseasePIP Phosphatidyl-Inositol-PhosphateSteatohepatitisqRT-PCR quantitative Real Time Polymerase Chain ReactionMice Knockoutlcsh:R5-920ORO Oil Red O StainingPI PhosphatidylinositolFatty liverTM6SF2 Transmembrane 6 Superfamily Member 2PhospholipidTAG TriglyceridesNASH Nonalcoholic SteatohepatitisLipogenesisLPA Lyso-Phosphatidic AcidPhosphatidylinositolSignal TransductionPS Phosphatidyl-SerinePA Palmitic AcidALD alcoholic liver diseasePC Phosphatidylcholinei.v. IntravenousFATP1 Fatty Acid Transport Protein 1Models BiologicalInternal medicinemedicineAnimalsNonalcoholic fatty liver diseasePPARα Peroxisome Proliferator-Activated Receptor alphaObesityG3P Glyceraldehyde-3-PhosphateSREBP1c Sterol Regulatory Element-Binding Protein 1HDL High Density Lipoproteinsbusiness.industryPI3K Phosphatidylinositol 3 KinaseMembrane ProteinsNHEJ Non-Homologues End JoiningPNPLA3 Patatin-like Phospholipase Domain-containing-3MTTP Microsomal Triglyceride Transfer ProteinLPIAT1 Lysophosphatidylinositol Acyltransferase 1TMC4 Transmembrane Channel-Like 4Disease Models AnimalGene Expression RegulationHepatocytesFOXA2 Forkhead Box A2mTOR mammalian target of RapamycinSteatosisInsulin ResistancebusinessPG Phosphatidyl-GlycerolFABP1 Fatty Acid-Binding Protein 1 FAS Fatty Acid SynthaseT2DM Type 2 Diabetes MellitusEBioMedicine
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Transmembrane 6 Superfamily Member 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis From Cardiovascular Disease

2015

Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed …

medicine.medical_specialtyHepatologymedicine.diagnostic_testbusiness.industryFatty liverOdds ratioHepatologymedicine.diseaseLower riskEndocrinologyInternal medicineLiver biopsyCohortmedicineSteatosisNASH TM6SF2businessTM6SF2
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GEMS, a GEnetic and Metabolic Staging predicting the outcome of non-alcoholic fatty liver disease

2021

Background and Aim: Non-alcoholic fatty liver disease(NAFLD) is an emergent cause of liver-related events(LRE). We have assessed the ability of a composite score based on clinical features, metabolic comorbidities and genetic background, to predict LRE. Methods: 546 consecutive patients with NAFLD were recruited and stratified according to FIB-4(low risk <1.3;intermedium-high risk ≥1.3). LRE were defined as occurrence of HCC or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LRE. Results: Over a median follow-up of 73.8 months, 58 patients experienced LRE(only 1 in the cohort of patients with FIB-4 65 years(HR 17.96), plat…

medicine.medical_specialtyMultivariate analysisHepatologyProportional hazards modelbusiness.industryFatty liverGastroenterologyNon alcoholicDiseasemedicine.diseaseOutcome (game theory)GastroenterologyHelsinki declarationHepatocellular carcinomaDiabetes mellitusInternal medicineCohortMedicinebusinessTM6SF2Digestive and Liver Disease
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