2007
Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance
Zhang D, Liu ZX, Choi CS, Tian L, Kibbey R, Dong J, Cline GW, Wood PA, Shulman GI. Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 17075-17080. PMID: 17940018, PMCID: PMC2040460, DOI: 10.1073/pnas.0707060104.Peer-Reviewed Original ResearchMeSH KeywordsAcyl Coenzyme AAcyl-CoA Dehydrogenase, Long-ChainAnimalsCalorimetryCarbon IsotopesDiglyceridesEnergy MetabolismFatty LiverGene Expression RegulationGlucoseHomeostasisInsulinInsulin ResistanceLiverMiceMitochondriaMuscle, SkeletalOxidation-ReductionProtein Kinase C-epsilonSignal TransductionTriglyceridesConceptsLong-chain acyl-CoA dehydrogenaseHepatic insulin resistanceInsulin stimulationMitochondrial functionInsulin resistanceMitochondrial fatty acid oxidation capacityMitochondrial fatty acid oxidationAcyl-CoA dehydrogenaseHepatic steatosisFatty acid oxidation capacityAkt2 activationDe novo synthesisFatty acid oxidationPKCepsilon activationKey enzymeHyperinsulinemic-euglycemic clampLong-chain acyl-CoA dehydrogenase deficiencyType 2 diabetesPrimary defectMitochondrial dysfunctionHepatic glucose productionAcyl-CoA dehydrogenase deficiencyPKCepsilon activityNovo synthesisDiacylglycerol accumulationn-3 Fatty Acids Preserve Insulin Sensitivity In Vivo in a Peroxisome Proliferator–Activated Receptor-α–Dependent Manner
Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher J, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI. n-3 Fatty Acids Preserve Insulin Sensitivity In Vivo in a Peroxisome Proliferator–Activated Receptor-α–Dependent Manner. Diabetes 2007, 56: 1034-1041. PMID: 17251275, DOI: 10.2337/db06-1206.Peer-Reviewed Original ResearchConceptsPPAR alpha-null miceHepatic insulin resistanceHigh-fat diet-induced hepatic insulin resistanceDiacylglycerol-dependent mannerInsulin resistanceWild-type miceFish oil dietOil dietPEPCK gene expressionNull miceDiet-induced hepatic insulin resistanceInsulin sensitivityPPAR-alpha nullSafflower oilFatty acidsGene expressionIsocaloric high-fat dietHigh-fat diet-induced insulin resistanceDiet-induced insulin resistancePeroxisome proliferator-activated receptorLipid abundanceFish oil replacementFish oilHigh-fat dietInsulin-mediated suppression
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