2010
Resistance to High-Fat Diet-Induced Obesity and Insulin Resistance in Mice with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency
Zhang D, Christianson J, Liu ZX, Tian L, Choi CS, Neschen S, Dong J, Wood PA, Shulman GI. Resistance to High-Fat Diet-Induced Obesity and Insulin Resistance in Mice with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. Cell Metabolism 2010, 11: 402-411. PMID: 20444420, PMCID: PMC3146169, DOI: 10.1016/j.cmet.2010.03.012.Peer-Reviewed Original ResearchConceptsMitochondrial fatty acid oxidationFatty acid oxidationMitochondrial fatty acid oxidation enzymesProtein kinase CthetaLong-chain acyl-CoA dehydrogenaseAcid oxidationFatty acid oxidation enzymesAcyl-CoA dehydrogenaseDiet-induced obesityMuscle insulin resistanceLong-Chain AcylInsulin resistanceCellular metabolismOxidation enzymesDiacylglycerol contentHigh-fat diet-induced obesityFat Diet-Induced ObesityType 2 diabetesImportant energy sourceCoA dehydrogenase deficiencyChronic activationInsulin sensitivity
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