2020
Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice
Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 32907986, PMCID: PMC7707176, DOI: 10.1194/jlr.ra119000586.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceInsulin resistanceHepatic insulin sensitivityHepatic steatosisLipid-induced hepatic insulin resistancePKCε activationInsulin sensitivityKnockout miceNormal hepatic insulin sensitivityWild-type control miceHepatic ceramide contentHyperinsulinemic-euglycemic clampComprehensive metabolic phenotypingLipid dropletsHepatic DAG contentDAG contentGlucose intoleranceControl miceMTTP activityHepatic insulinAnimal modelsSteatosisAKT Ser/ThrMiceMetabolic phenotyping
2019
266-OR: Plasma Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance
LYU K, ZHANG Y, ZHANG D, KAHN M, NOZAKI Y, BHANOT S, BOGAN J, CLINE G, SAMUEL V, SHULMAN G. 266-OR: Plasma Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance. Diabetes 2019, 68 DOI: 10.2337/db19-266-or.Peer-Reviewed Original ResearchHepatic insulin resistanceInsulin resistanceExogenous fatty acidsInsulin actionLipid dropletsHepatic ceramide contentHyperinsulinemic-euglycemic clampHepatic insulin actionBioactive lipid speciesHepatic glucose productionChow-fed ratsHepatic diacylglycerol contentAdvisory PanelFatty acidsHepatic steatosisImpaired suppressionSingle doseSpouse/partnerGlucose productionPKCε activationJanssen ResearchAcute knockdownCeramide contentNational InstituteReceptor kinase activation
2013
CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance
Cantley JL, Yoshimura T, Camporez JP, Zhang D, Jornayvaz FR, Kumashiro N, Guebre-Egziabher F, Jurczak MJ, Kahn M, Guigni BA, Serr J, Hankin J, Murphy RC, Cline GW, Bhanot S, Manchem VP, Brown JM, Samuel VT, Shulman GI. CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1869-1874. PMID: 23302688, PMCID: PMC3562813, DOI: 10.1073/pnas.1219456110.Peer-Reviewed Original ResearchMeSH Keywords1-Acylglycerol-3-Phosphate O-AcyltransferaseAdipose Tissue, WhiteAnimalsCell MembraneDiet, High-FatDiglyceridesEndoplasmic ReticulumGene ExpressionGene Knockdown TechniquesHumansImmunoblottingInjections, IntraperitonealInsulin ResistanceLipidsLiverMaleMiceMice, Inbred C57BLOligonucleotides, AntisenseProtein Kinase C-epsilonProtein TransportReverse Transcriptase Polymerase Chain ReactionConceptsHepatic insulin resistanceInsulin resistanceHepatic steatosisCGI-58 knockdownHigh-fat fed miceHyperinsulinemic-euglycemic clamp studiesSevere hepatic steatosisCGI-58 expressionFat-fed miceLipid-induced hepatic insulin resistanceChanarin-Dorfman syndromeComparative gene identification-58Lipid droplet-associated proteinAdipose triglyceride lipaseDroplet-associated proteinAntisense oligonucleotide treatmentInsulin sensitivityASO treatmentClamp studiesLipotoxic conditionsKnockdown miceCGI-58PKCε activationMiceTriglyceride lipase