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
2012
Fatty acid amide hydrolase ablation promotes ectopic lipid storage and insulin resistance due to centrally mediated hypothyroidism
Brown WH, Gillum MP, Lee HY, Camporez JP, Zhang XM, Jeong JK, Alves TC, Erion DM, Guigni BA, Kahn M, Samuel VT, Cravatt BF, Diano S, Shulman GI. Fatty acid amide hydrolase ablation promotes ectopic lipid storage and insulin resistance due to centrally mediated hypothyroidism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 14966-14971. PMID: 22912404, PMCID: PMC3443187, DOI: 10.1073/pnas.1212887109.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAmidohydrolasesAnalysis of VarianceAnimalsArachidonic AcidsChromatography, LiquidEndocannabinoidsEnergy MetabolismEthanolaminesHypothyroidismImmunoblottingInsulin ResistanceMiceMice, KnockoutPalmitic AcidsPolymerase Chain ReactionPolyunsaturated AlkamidesPPAR gammaTandem Mass SpectrometryThyrotropinThyrotropin-Releasing HormoneThyroxineTriiodothyronineConceptsEctopic lipid storageHepatic insulin resistanceInsulin resistanceEnergy expenditureDiet-induced hepatic insulin resistanceHypothalamic thyrotropin-releasing hormoneFatty acid amide hydrolase knockout miceThyroid-stimulating hormoneThyrotropin-releasing hormoneLipid storageDeiodinase 2 expressionReduced mRNA expressionProtein kinase Cε activationHepatic diacylglycerol contentPituitary thyroid-stimulating hormoneExcess energy storageFAAH deletionKnockout miceReceptor γThyroid axisThyroxine concentrationsMRNA expressionMiceHypothyroidismFAAH
2011
Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease
Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X, Still CD, Gerhard GS, Han X, Dziura J, Petersen KF, Samuel VT, Shulman GI. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 16381-16385. PMID: 21930939, PMCID: PMC3182681, DOI: 10.1073/pnas.1113359108.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseFatty liver diseaseHepatic DAG contentInsulin resistanceHepatic insulin resistanceLiver diseaseHepatic steatosisCellular mechanismsHomeostatic model assessmentInsulin resistance indexMarkers of inflammationType 2 diabetesER stress markersLipid dropletsHepatic diacylglycerol contentEndoplasmic reticulum stressActivation of PKCεLiver biopsyNondiabetic individualsHepatocellular lipidsInsulin sensitivityCytoplasmic lipid dropletsDAG contentResistance indexAnimal models
2007
Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance*
Choi CS, Savage DB, Kulkarni A, Yu XX, Liu ZX, Morino K, Kim S, Distefano A, Samuel VT, Neschen S, Zhang D, Wang A, Zhang XM, Kahn M, Cline GW, Pandey SK, Geisler JG, Bhanot S, Monia BP, Shulman GI. Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance*. Journal Of Biological Chemistry 2007, 282: 22678-22688. PMID: 17526931, DOI: 10.1074/jbc.m704213200.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseHepatic insulin resistanceProtein kinase C epsilon activationInsulin resistanceASO treatmentFat-induced hepatic insulin resistanceDiet-induced nonalcoholic fatty liver diseaseDiacylglycerol acyltransferase 2Epsilon activationHigh fat-fed ratsTriglyceride synthesisFatty liver diseaseType 2 diabetesHepatic fatty acid oxidationHepatic insulin sensitivityFat-fed ratsFatty acid oxidationHepatic diacylglycerol contentLiver diseaseHepatic lipidsHepatic steatosisControl ratsInsulin sensitivityPharmacological reductionParadoxical reduction