2023
Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice
Makhlouf M, Souza D, Kurian S, Bellaver B, Ellis H, Kuboki A, Al-Naama A, Hasnah R, Venturin G, da Costa J, Venugopal N, Manoel D, Mennella J, Reisert J, Tordoff M, Zimmer E, Saraiva L. Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice. Molecular Metabolism 2023, 79: 101837. PMID: 37977411, PMCID: PMC10724696, DOI: 10.1016/j.molmet.2023.101837.Peer-Reviewed Original ResearchConceptsMacronutrient contentIncrease food safetyGrain-based dietShort-term consumptionElectro-olfactogramFood safetyProcessed dietsFood processingBrain regionsBrain metabolismOdor-guided behaviorStandard chow dietShort-term intakeDietGlucose metabolism imagingHigh-fat dietFoodResponses to odorantsBrain glucose metabolismOlfactory mucosaModern dietFood consumptionChow dietChronic consumptionMetabolic phenotype192-OR: Lipid-Induced Insulin Resistance in Brown Adipose Tissue Is Mediated by the sn-1,2 DAG-PKCe-IRKT1150 Phosphorylation Pathway
GASPAR R, HUBBARD B, SAKUMA I, LAMOIA T, ZHANG D, SHULMAN G. 192-OR: Lipid-Induced Insulin Resistance in Brown Adipose Tissue Is Mediated by the sn-1,2 DAG-PKCe-IRKT1150 Phosphorylation Pathway. Diabetes 2023, 72 DOI: 10.2337/db23-192-or.Peer-Reviewed Original ResearchModulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis
Liao C, Barrow F, Venkatesan N, Nakao Y, Mauer A, Fredrickson G, Song M, Sehrawat T, Dasgupta D, Graham R, Revelo X, Malhi H. Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis. Frontiers In Immunology 2023, 14: 1130184. PMID: 37153573, PMCID: PMC10160388, DOI: 10.3389/fimmu.2023.1130184.Peer-Reviewed Original ResearchConceptsMurine nonalcoholic steatohepatitisNonalcoholic steatohepatitisLiver injuryHepatic macrophage accumulationT cellsIntrahepatic leukocytesDietary feedingNKT cellsMacrophage accumulationReceptor antagonismLeukocyte populationsB cellsDouble-negative T cellsReceptor-specific modulationNegative T cellsStandard chow dietImmune cell populationsC57BL/6 male miceCirculating MarkersLiver histologyProinflammatory markersNK cellsOral gavageChow dietNASH progression
2022
The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice
Cootes T, Bhattacharyya N, Huang S, Daniel L, Bell-Anderson K, Stifter S, Chew T, Solon-Biet S, Saraiva L, Cai Y, Chen X, Simpson S, Feng C. The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice. Cell Reports 2022, 41: 111638. PMID: 36384123, DOI: 10.1016/j.celrep.2022.111638.Peer-Reviewed Original ResearchConceptsGrain-based chow dietOutcome of host-pathogen interactionsSusceptibility to influenzaHost resistance to infectionInterferon (IFN)-gHost-pathogen interactionsMortality to infectionDiet compositionInfluenza infectionResistance to infectionHost phenotypeChow dietInfection susceptibilityHost defenseImpact of diet compositionExtrinsic signalsMiceLaboratory rodent dietHeightened susceptibilityInfectionAdaptive homeostasisAIN93GRodent dietIndividual macronutrientsInfluenza
2021
Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis
Price NL, Zhang X, Fernández-Tussy P, Singh AK, Burnap SA, Rotllan N, Goedeke L, Sun J, Canfrán-Duque A, Aryal B, Mayr M, Suárez Y, Fernández-Hernando C. Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2006478118. PMID: 33495342, PMCID: PMC7865172, DOI: 10.1073/pnas.2006478118.Peer-Reviewed Original ResearchConceptsMiR-33 deficiencyHDL-C levelsMiR-33Body weightAtherosclerotic plaque sizeAtherosclerotic plaque burdenDevelopment of fibrosisCholesterol transport capacityCholesterol transporter ABCA1High-density lipoprotein biogenesisSREBP2 transcription factorKnockout mouse modelConditional knockout mouse modelPlaque burdenCardiometabolic diseasesChow dietLiver functionMetabolic dysfunctionHDL metabolismHyperlipidemic conditionsMouse modelGlucose homeostasisCholesterol effluxLipid metabolismObesity
2020
Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease
Kim TH, Banini BA, Asumda FZ, Campbell NA, Hu C, Moser CD, Shire AM, Han S, Ma C, Krishnan A, Mounajjed T, White TA, Gores GJ, LeBrasseur NK, Charlton MR, Roberts LR. Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease. AJP Gastrointestinal And Liver Physiology 2020, 319: g333-g344. PMID: 32683952, PMCID: PMC7509257, DOI: 10.1152/ajpgi.00150.2019.Peer-Reviewed Original ResearchConceptsFast food dietStandard chow dietWT miceDiet-induced steatohepatitisNonalcoholic steatohepatitisSulfatase 2Hepatic fibrosisMouse modelStandard chow diet ad libitumChow diet ad libitumNonalcoholic fatty liver diseaseDiet-induced mouse modelConditions of overnutritionProtein expressionFatty liver diseasePotential therapeutic mechanismWild-type miceDiet ad libitumThreefold increaseLiver diseaseChow dietKO miceLiver fibrosisSteatohepatitisMurine model
2019
Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet
Minuzzi L, Kuga G, Breda L, Gaspar R, Muñoz V, Pereira R, Botezelli J, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet. Experimental And Clinical Endocrinology & Diabetes 2019, 128: 30-37. PMID: 30991419, DOI: 10.1055/a-0885-9872.Peer-Reviewed Original ResearchConceptsLong-term high-fat dietShort-term resistance trainingHigh-fat dietResistance trainingInsulin sensitivityHigh calorie intakeLiver of miceAdiponectin pathwayChow dietMice fedInsulin resistanceGlycemic homeostasisSwiss miceAdiponectin receptorsPhysical activityPhysical exerciseInsulin actionHepatic tissueMiceLiverDietAdiponectinInadequate levelsAdverse consequencesCritical regulator
2018
Genetically Obese Human Gut Microbiota Induces Liver Steatosis in Germ-Free Mice Fed on Normal Diet
Wang R, Li H, Yang X, Xue X, Deng L, Shen J, Zhang M, Zhao L, Zhang C. Genetically Obese Human Gut Microbiota Induces Liver Steatosis in Germ-Free Mice Fed on Normal Diet. Frontiers In Microbiology 2018, 9: 1602. PMID: 30079055, PMCID: PMC6062601, DOI: 10.3389/fmicb.2018.01602.Peer-Reviewed Original ResearchHepatic transcriptional profilePreM groupGut microbiotaLiver steatosisNon-alcoholic fatty liver diseaseDietary weight loss programObesity-associated gut microbiotaLipid metabolismPeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaDysbiotic gut microbiotaLiver macrovesicular steatosisFatty liver diseaseNormal chow dietWeight loss programC57BL/6J male miceNormal hepatic physiologyObese human donorsLiver diseaseChow dietLoss programMice fedHuman gut microbiotaMacrovesicular steatosisMetabolic deteriorationMembrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance In Vivo
LYU K, ZHANG D, NOZAKI Y, ZHANG Y, BHANOT S, CLINE G, SAMUEL V, SHULMAN G. Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance In Vivo. Diabetes 2018, 67 DOI: 10.2337/db18-243-lb.Peer-Reviewed Original ResearchHepatic insulin resistanceLipid-induced hepatic insulin resistanceDiglyceride acyltransferase 2Hepatic DAG contentInsulin resistanceHepatic insulin sensitivityInsulin sensitivityImpaired insulin-mediated suppressionActivation/translocationDGAT2 inhibitionAntisense oligonucleotideRegular chow dietInsulin-mediated suppressionHepatic insulin actionHepatic glucose productionInsulin receptor kinaseDAG contentChow dietASO treatmentIonis PharmaceuticalsInsulin actionGlucose productionPKCε activationSREBP-1cGilead Sciences
2017
The Transcriptomic Signature Of Disease Development And Progression Of Nonalcoholic Fatty Liver Disease
Cazanave S, Podtelezhnikov A, Jensen K, Seneshaw M, Kumar DP, Min HK, Santhekadur PK, Banini B, Mauro AG, M. Oseini A, Vincent R, Tanis KQ, Webber AL, Wang L, Bedossa P, Mirshahi F, Sanyal AJ. The Transcriptomic Signature Of Disease Development And Progression Of Nonalcoholic Fatty Liver Disease. Scientific Reports 2017, 7: 17193. PMID: 29222421, PMCID: PMC5722878, DOI: 10.1038/s41598-017-17370-6.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseFatty liver diseaseAdvanced fibrosisLiver diseaseMacrophage activationPathway activationHepatic stellate cell activationFatty liver developmentStellate cell activationOxidative stress pathwaysCell deathAdvanced diseaseMetabolic pathway activationChow dietFatty liverEarly fibrosisFibrogenic pathwaysCell stressSuch miceAnimal modelsCell activationFibrosisMetabolic perturbationsDiseaseOxidative stress
2016
A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer
Asgharpour A, Cazanave SC, Pacana T, Seneshaw M, Vincent R, Banini BA, Kumar DP, Daita K, Min HK, Mirshahi F, Bedossa P, Sun X, Hoshida Y, Koduru SV, Contaifer D, Warncke UO, Wijesinghe DS, Sanyal AJ. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. Journal Of Hepatology 2016, 65: 579-588. PMID: 27261415, PMCID: PMC5012902, DOI: 10.1016/j.jhep.2016.05.005.Peer-Reviewed Original ResearchConceptsNon-alcoholic steatohepatitisNon-alcoholic fatty liver diseaseDiet-induced animal modelsProgressive non-alcoholic steatohepatitisHuman non-alcoholic steatohepatitisFatty liver diseaseHepatocellular cancerLiver diseaseAnimal modelsDiet-induced mouse modelGene signatureHigh-fat dietSimilar histological phenotypesAd libitum consumptionProgressive fibrosisLDL cholesterolChow dietMice fedInsulin resistanceFat dietClinical endpointsHuman NAFLDObesogenic dietPreclinical modelsMouse model
2012
The role of p21-activated kinase in the initiation of atherosclerosis
Jhaveri K, Debnath P, Chernoff J, Sanders J, Schwartz M. The role of p21-activated kinase in the initiation of atherosclerosis. BMC Cardiovascular Disorders 2012, 12: 55. PMID: 22824149, PMCID: PMC3489605, DOI: 10.1186/1471-2261-12-55.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesAtherosclerosisBiomechanical PhenomenaCells, CulturedDisease Models, AnimalEndothelial CellsFibronectinsGalectin 3ImmunohistochemistryInflammation MediatorsIntercellular Adhesion Molecule-1MaleMiceMice, Inbred C57BLMice, Knockoutp21-Activated KinasesRegional Blood FlowTranscription Factor RelBVascular Cell Adhesion Molecule-1ConceptsLesser curvatureNF-κB subunitsInflammatory activationEndothelial cellsAtherosclerosis-prone sitesPro-inflammatory functionsInflammatory marker expressionNormal chow dietArch of aortaInitiation of atherosclerosisInflammatory markersOverall inflammationChow dietInflammatory pathwaysYoung miceAtherosclerosis-susceptible regionsConclusionThese dataICAM-1VCAM-1NF-κBRelA NF-κB subunitMarker expressionLow levelsFibronectin depositionInflammation
2011
Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output
Baghdasaryan A, Claudel T, Gumhold J, Silbert D, Adorini L, Roda A, Vecchiotti S, Gonzalez FJ, Schoonjans K, Strazzabosco M, Fickert P, Trauner M. Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output. Hepatology 2011, 54: 1303-1312. PMID: 22006858, PMCID: PMC3744065, DOI: 10.1002/hep.24537.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnalysis of VarianceAnimalsAnion Transport ProteinsATP Binding Cassette Transporter, Subfamily BBile Acids and SaltsBiliary Tract DiseasesCholic AcidsDisease Models, AnimalLiver DiseasesMaleMiceMice, Inbred C57BLRandom AllocationReceptors, Cytoplasmic and NuclearReceptors, G-Protein-CoupledStatistics, NonparametricConceptsFarnesoid X receptorINT-767Liver injuryChronic cholangiopathiesTGR5 agonistsINT-747Hepatic inflammationINT-777Bile secretionBiliary bile acid outputActivation of FXRNuclear farnesoid X receptorSerum liver enzymesBile acid outputBile acid homeostasisFXR-dependent mannerBile acid synthesisMembrane G protein-coupled receptorsG protein-coupled receptorsLiver transplantationProtein-coupled receptorsBiliary fibrosisAcid outputChow dietTherapeutic options
2010
Deletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity
Chutkow WA, Birkenfeld AL, Brown JD, Lee HY, Frederick DW, Yoshioka J, Patwari P, Kursawe R, Cushman SW, Plutzky J, Shulman GI, Samuel VT, Lee RT. Deletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity. Diabetes 2010, 59: 1424-1434. PMID: 20299477, PMCID: PMC2874703, DOI: 10.2337/db09-1212.Peer-Reviewed Original ResearchConceptsTxnip knockout miceInsulin resistanceInsulin sensitivityKnockout miceInsulin responsivenessTXNIP expressionSkeletal muscleWild-type littermate control miceStandard chow dietType 2 diabetes pathogenesisHigh-fat dietHigh-fat feedingLittermate control miceGene-deleted miceInhibits glucose uptakeControl miceChow dietAdipose massMore insulinCaloric excessFat massDiabetes pathogenesisMouse embryonic fibroblastsRegulator of adipogenesisPPARgamma expression
2009
Prolylcarboxypeptidase regulates food intake by inactivating α-MSH in rodents
Wallingford N, Perroud B, Gao Q, Coppola A, Gyengesi E, Liu ZW, Gao XB, Diament A, Haus KA, Shariat-Madar Z, Mahdi F, Wardlaw SL, Schmaier AH, Warden CH, Diano S. Prolylcarboxypeptidase regulates food intake by inactivating α-MSH in rodents. Journal Of Clinical Investigation 2009, 119: 2291-2303. PMID: 19620781, PMCID: PMC2719925, DOI: 10.1172/jci37209.Peer-Reviewed Original ResearchConceptsFood intakeHigh-fat diet-induced obesityReduced body fatRegular chow dietDiet-induced obesityPRCP activityWild-type controlsChow dietMelanocortin signalingObese miceWeight maintenanceReal-time PCRAxon terminalsBody fatNeuronal populationsΑ-MSHBrain tissueMRNA expressionMouse strainsSmall molecule protease inhibitorsElevated levelsVivo activityProlylcarboxypeptidaseProtease inhibitorsHypothalamus
2007
THE ANTI‐ANGIOGENIC ACTIVITY OF rPAI‐123 INHIBITS ANGIOGENIC VASA VASORUM AND ATHERSCLEROTIC PLAQUE GROWTH
Mulligan‐Kehoe M, Drinane M, Mollmark J, Simons M. THE ANTI‐ANGIOGENIC ACTIVITY OF rPAI‐123 INHIBITS ANGIOGENIC VASA VASORUM AND ATHERSCLEROTIC PLAQUE GROWTH. The FASEB Journal 2007, 21: a16-a17. DOI: 10.1096/fasebj.21.5.a16-d.Peer-Reviewed Original ResearchHigh-fat dietAnti-angiogenic activityVasa vasorumPlaque growthSaline treatmentPlaque areaPlaque progressionLumen areaRole of angiogenesisVasa vasorum densitySignificant anti-angiogenic activityAtherogenic micePlaque regressionHFD groupNeovascularized areaChow dietPAI-1 proteinFat dietAortic rootControl animalsVessel circumferenceVasorumVessel areaMiceReconstructed vessels
2004
Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle
Kim JK, Gimeno RE, Higashimori T, Kim HJ, Choi H, Punreddy S, Mozell RL, Tan G, Stricker-Krongrad A, Hirsch DJ, Fillmore JJ, Liu ZX, Dong J, Cline G, Stahl A, Lodish HF, Shulman GI. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle. Journal Of Clinical Investigation 2004, 113: 756-763. PMID: 14991074, PMCID: PMC351314, DOI: 10.1172/jci18917.Peer-Reviewed Original ResearchMeSH KeywordsAdiponectinAdipose TissueAnimalsBlood GlucoseCarrier ProteinsDiabetes Mellitus, Type 2Fatty Acid Transport ProteinsFatty AcidsFemaleGene DeletionGene Expression RegulationGlucoseInsulinInsulin ResistanceIntercellular Signaling Peptides and ProteinsMaleMembrane Transport ProteinsMiceMice, KnockoutModels, GeneticMuscle, SkeletalPatch-Clamp TechniquesPhenotypeProteinsSignal TransductionConceptsFatty acid transport protein 1Fatty acid metabolitesInsulin resistanceType 2 diabetesWhole-body adiposityKO miceAcid metabolitesSkeletal muscleChronic high-fat feedingAcute lipid infusionRegular chow dietHigh-fat feedingNovel therapeutic targetFatty acid uptakeIntramuscular accumulationLipid infusionChow dietInsulin sensitivityGlucose homeostasisTherapeutic targetInsulin actionAcid uptakeProtein 1Tissue expressionMice
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