0000000000217654

AUTHOR

Raffaela Rametta

showing 10 related works from this author

Protein phosphatase 1 regulatory subunit 3B gene variation protects against hepatic fat accumulation and fibrosis in individuals at high risk of nona…

2018

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver damage and has a strong genetic component. The rs4841132 G>A variant, modulating the expression of protein phosphatase 1 regulatory subunit 3B (PPP1R3B), which is involved in glycogen synthesis, has been reported to reduce the risk of NAFLD but at the same time may favor liver disease by facilitating glycogen accumulation. The aim of this study was to assess the impact of rs4841132 on development of histologic steatosis and fibrosis in 1,388 European individuals in a liver biopsy cohort, on NAFLD hepatocellular carcinoma in a cross-sectional Italian cohort (n = 132 cases), and on liver disease at the population level in the …

0301 basic medicinemedicine.medical_specialtySettore MED/12 - GASTROENTEROLOGIAPopulation03 medical and health sciencesLiver disease0302 clinical medicineLipid oxidationFibrosisInternal medicineNonalcoholic fatty liver diseasemedicineeducationNASH NAFLDeducation.field_of_studyHepatologymedicine.diagnostic_testbusiness.industryOriginal ArticlesHepatologymedicine.diseasen/a030104 developmental biologyEndocrinologyLiver biopsy030211 gastroenterology & hepatologyOriginal ArticleSteatosisbusiness
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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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PCSK9 rs11591147 R46L loss-of-function variant protects against liver damage in individuals with NAFLD

2020

Background and Aims: The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower low-density lipoprotein cholesterol (LDL-C) levels. In this study, we examined the impact of the PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models. Methods: We considered 1874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9, was genotyped by TaqMan assays. We also evaluated 1) PCSK9 mRNA…

Malemedicine.medical_specialtyProprotein Convertase 9.GastroenterologyPCSK903 medical and health sciencesMice0302 clinical medicineFibrosisNon-alcoholic Fatty Liver DiseaseSettore BIO/13 - Biologia ApplicataInternal medicineNonalcoholic fatty liver diseaseMedicineSNPAnimalsHumansFIBROSISLoss functionSettore MED/12 - GastroenterologiaHepatologybusiness.industryAnimalPCSK9ConfoundingNASHCholesterol LDLProprotein convertasemedicine.diseaseLiver030220 oncology & carcinogenesisKexin030211 gastroenterology & hepatologyProprotein Convertase 9businessHuman
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Prevalence and Risk Factors of Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Without Steatohepatitis

2019

In patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is a risk factor for the development of fibrosis. However, fibrosis has been observed in livers of patients without NASH. We aimed to estimate the prevalence of fibrosis in patients without NASH and risk factors for fibrosis.We analyzed data from 1738 subjects (44.9% with severe obesity) in a cross-sectional liver biopsy cohort enrolled at referral centers in Italy and Finland. Biopsy specimens were analyzed histologically by a blinded pathologist at each center, and a diagnosis of NASH was made based on steatosis (≥5% of hepatocytes), hepatocellular ballooning, and lobular inflammation. We also c…

AdultLiver CirrhosisMalemedicine.medical_specialtyBiopsydigestive systemGastroenterologyRisk Assessment03 medical and health sciences0302 clinical medicineFibrosisNon-alcoholic Fatty Liver DiseaseInternal medicineNonalcoholic fatty liver diseaseBiopsymedicinePrevalenceHumansrisk factorsRisk factorhistory; inflammatory response; progression; risk factorsHepatologymedicine.diagnostic_testbusiness.industryFatty liverGastroenterologynutritional and metabolic diseasesinflammatory responsemedicine.diseasedigestive system diseasesFatty LiverCross-Sectional StudiesItalyLiver030220 oncology & carcinogenesisLiver biopsyCohort030211 gastroenterology & hepatologyFemalehistoryprogressionSteatohepatitisbusiness
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Statin use and non-alcoholic steatohepatitis in at risk individuals.

2015

Background & Aims Excess hepatic free cholesterol contributes to the pathogenesis of non-alcoholic steatohepatitis, and statins reduce cholesterol synthesis. Aim of this study was to assess whether statin use is associated with histological liver damage related to steatohepatitis. Methods The relationship between statin use, genetic risk factors, and liver damage was assessed in a multi-center cohort of 1201 European individuals, who underwent liver biopsy for suspected non-alcoholic steatohepatitis. Results Statin use was recorded in 107 subjects, and was associated with protection from steatosis, NASH, and fibrosis stage F2-F4, in a dose-dependent manner (adjusted p <0.05 for all).…

AdultMaleRiskmedicine.medical_specialtyStatinmedicine.drug_classBiopsyGastroenterologyNon-alcoholic Fatty Liver DiseaseInternal medicinemedicineHumansSteatosiPNPLA3AgedHepatologymedicine.diagnostic_testbusiness.industryNASHStatinMembrane ProteinsLipaseHepatologyMiddle AgedImpaired fasting glucosemedicine.diseaseCholesterolEndocrinologyLogistic ModelsLiverLiver biopsyCohortFemaleSteatosisSteatohepatitisHydroxymethylglutaryl-CoA Reductase InhibitorsbusinessNon-alcoholic steatohepatitiTM6SF2Journal of hepatology
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<i>PCSK9</i> rs11591147 R46L Loss-of-Function Variant Protects Against Liver Damage in Individuals with NAFLD

2020

Background and Aims: The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower LDL-C levels. In this study, we examined the impact of PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models. Methods: We considered 1,874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9, was genotyped by TaqMan assays. We also evaluated 1) PCSK9 mRNA hepatic expression in human liver, and 2…

medicine.medical_specialtyHuman liverbusiness.industryPCSK9Helsinki declarationFat accumulationInformed consentInternal medicineMedicinemedia_common.cataloged_instanceLiver damageEuropean unionbusinessPharmacogeneticsmedia_commonSSRN Electronic Journal
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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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PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients

2019

Dyslipidemia and altered iron metabolism are typical features of nonalcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7) gene variation has been associated with circulating lipids and liver damage during iron overload. The aim of this study was to examine the impact of the PCSK7 rs236918 variant on NAFLDrelated traits in 1,801 individuals from the Liver Biopsy Cohort (LBC), 500,000 from the UK Biobank Cohort (UKBBC), and 4,580 from the Dallas Heart Study (DHS). The minor PCSK7 rs236918 C allele was associated with higher triglycerides, aminotransferases, and hepatic inflammation in the LBC (P < 0.05) and with hypercholesterolemia and liver disease …

0301 basic medicinenonalcoholic fatty liver diseasemedicine.medical_specialtyDyslipidemias; Genetics; Inflammation; Liver; Triglycerides; genes in lipid dysfunction; metabolic disease; non-alcoholic fatty liver diseaseHyperlipidemiasInflammationQD415-436030204 cardiovascular system & hematologyBiochemistryproprotein convertase subtilisin/kexin type 703 medical and health sciencesLiver disease0302 clinical medicineEndocrinologyGeneticInternal medicineNonalcoholic fatty liver diseasemedicineGeneticsHumansSubtilisinsAlleleTriglyceridesDyslipidemiasHypertriglyceridemiaInflammationgenes in lipid dysfunctionmedicine.diagnostic_testbusiness.industrynon-alcoholic fatty liver diseaseCell Biologymedicine.diseasemetabolic disease030104 developmental biologyEndocrinologyLiverLiver biopsyLipogenesisKexinmedicine.symptomPatient-Oriented and Epidemiological ResearchbusinessDyslipidemia
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MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease

2015

Background & Aim Homozygosity for a common non-coding rs4374383 G>A polymorphism in MERTK (myeloid-epithelial-reproductive tyrosine kinase) has been associated with the protection against fibrosis progression in chronic hepatitis C. The main study objective was to assess whether MERTK AA genotype influences liver fibrosis, and secondarily MERTK expression in patients with non-alcoholic fatty liver disease (NAFLD). We also investigated whether MERTK is expressed in human hepatic stellate cells (HSC) and in murine models of fibrogenesis. Methods We considered 533 consecutive patients who underwent liver biopsy for suspected non-alcoholic steatohepatitis (NASH) without severe obesity from two …

Liver CirrhosisMale0301 basic medicineMessengerMice0302 clinical medicineNon-alcoholic Fatty Liver DiseaseFibrosisInbred BALB CCells CulturedMice Inbred BALB CCulturedmedicine.diagnostic_testMedicine (all)Fatty liverNASHMiddle AgedLiver biopsyFemale030211 gastroenterology & hepatologyAdultmedicine.medical_specialtyMERTKCellsBiology03 medical and health sciencesGeneticProto-Oncogene ProteinsInternal medicinemedicineAnimalsHumansFibrosis; MERTK; NASH; Adult; Animals; Cells Cultured; Female; Humans; Liver Cirrhosis; Male; Mice Inbred BALB C; Middle Aged; Non-alcoholic Fatty Liver Disease; Proto-Oncogene Proteins; RNA Messenger; Receptor Protein-Tyrosine Kinases; Polymorphism Genetic; Medicine (all); HepatologyRNA MessengerPolymorphismPolymorphism Geneticc-Mer Tyrosine KinaseHepatologyGAS6Receptor Protein-Tyrosine Kinasesnafld fibrosis mertkMERTKHepatologymedicine.diseaseFibrosis030104 developmental biologyImmunologyHepatic stellate cellRNASteatohepatitisJournal of Hepatology
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The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis

2015

Background & Aims Uncoupling protein 2 - UCP2 - regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The −866 G>A UCP2 promoter region polymorphism has been linked to insulin resistance and lipid metabolism. The aim of this study was to assess whether the −866 G>A UCP2 polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP2 expression. Methods We considered 688 Italian patients who underwent liver biopsy for suspected NASH, and 232 healthy controls. The UCP2 −866 G>A polymorphism was determined by allele specific oligonucleotide probes, hepatic UCP2 mRNA levels …

AdultMalemedicine.medical_specialtyGenotypeRespiratory chainGene ExpressionBiologyIon ChannelsMitochondrial Proteinsgenetic polymorphism; lipid metabolism;liver; mitochondria; nonalcoholic steatohepatitis; uncoupling protein-2Insulin resistanceNon-alcoholic Fatty Liver DiseaseRisk FactorsDiabetes mellitusInternal medicineGenotypemedicineHumansUncoupling Protein 2Promoter Regions GeneticUncoupling protein-2AllelesAgedPolymorphism GeneticGenetic polymorphismmedicine.diagnostic_testHepatologyLipid metabolismMiddle Agedmedicine.diseaseImpaired fasting glucoseMitochondriaEndocrinologyLogistic ModelsLipid metabolismLiverLiver biopsyCase-Control StudiesFemaleSteatosisInsulin ResistanceNonalcoholic steatohepatiti
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