2020
Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance
He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. Journal Of Experimental Medicine 2020, 218: e20201416. PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAnimalsDiabetes Mellitus, Type 2Diet, High-FatEnergy MetabolismFatty LiverGene DeletionGene TargetingGluconeogenesisHomeostasisHumansHyperglycemiaInflammationInsulin ResistanceLipogenesisLiverMaleMice, Inbred C57BLMice, KnockoutMitochondriaMitophagyNF-kappa BOxidative StressPhenotypeReactive Oxygen SpeciesSequestosome-1 ProteinSignal TransductionThioredoxinsConceptsHepatic insulin resistanceWhite adipose tissueInsulin resistanceAdipose inflammationType 2 diabetes mellitusLipid metabolic disordersNF-κB inhibitorAdipose-specific deletionWhole-body energy homeostasisAltered fatty acid metabolismFatty acid metabolismT2DM progressionT2DM patientsDiabetes mellitusReactive oxygen species pathwayHepatic steatosisMetabolic disordersNF-κBP62/SQSTM1Adipose tissueHuman adipocytesEnergy homeostasisExcessive mitophagyOxygen species pathwayInflammationOne-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension
Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, Jorgensen JA, Schaart G, Zhang D, Meijer K, Hopman M, Hesselink MKC, Ouwens DM, Shulman GI, Schrauwen-Hinderling VB, Schrauwen P. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia 2020, 63: 1211-1222. PMID: 32185462, PMCID: PMC7228997, DOI: 10.1007/s00125-020-05128-1.Peer-Reviewed Original ResearchConceptsMitochondrial oxidative capacityLow mitochondrial oxidative capacityLipid infusionInsulin resistancePhysical inactivityOxidative capacityLipid-induced insulin resistanceUnilateral lower limb suspensionConclusions/interpretationTogetherIntramyocellular lipid depositionMusculus tibialis anteriorChronic metabolic disorderIntramyocellular lipid accumulationType 2 diabetesReduced insulin sensitivityMuscle fat accumulationMusculus vastus lateralisMitochondrial functionUnilateral limb suspensionIMCL contentContralateral legInsulin sensitivityResultsIn vivoTibialis anteriorFat accumulation
2019
Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates
Goedeke L, Peng L, Montalvo-Romeral V, Butrico GM, Dufour S, Zhang XM, Perry RJ, Cline GW, Kievit P, Chng K, Petersen KF, Shulman GI. Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates. Science Translational Medicine 2019, 11 PMID: 31578240, PMCID: PMC6996238, DOI: 10.1126/scitranslmed.aay0284.Peer-Reviewed Original ResearchConceptsControlled-release mitochondrial protonophoreNonalcoholic fatty liver diseaseCRMP treatmentHepatic triglyceridesDiet-induced rodent modelReversal of hypertriglyceridemiaFatty liver diseaseNonhuman primate modelMitochondrial protonophoreEndogenous glucose productionLow-density lipoproteinMitochondrial fat oxidationHepatic inflammationMetabolic syndromeFatty liverLiver diseaseHepatic steatosisInsulin resistanceAdverse reactionsPlasma triglyceridesPrimate modelOral administrationFood intakeHepatic mitochondrial oxidationRodent models
2015
Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*
Camell CD, Nguyen KY, Jurczak MJ, Christian BE, Shulman GI, Shadel GS, Dixit VD. Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*. Journal Of Biological Chemistry 2015, 290: 29402-29413. PMID: 26438821, PMCID: PMC4705943, DOI: 10.1074/jbc.m115.680199.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBone Marrow CellsCarrier ProteinsCeramidesDiet, High-FatDisease Models, AnimalFatty AcidsFemaleInflammasomesInflammationInsulin ResistanceLipidsMacrophagesMaleMiceMice, TransgenicMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinObesityOxidative StressSerine C-PalmitoyltransferaseConceptsDe novo synthesisNovo synthesisOverexpression of catalaseDietary lipid overloadSynthesis machineryTissue homeostasisCell-specific deletionInflammasome activationAdipose tissue homeostasisNLRP3 inflammasome activationMyeloid cell-specific deletionMetabolic pathwaysCeramide synthesisAlternate metabolic pathwaysCaspase-1 cleavageEnergy homeostasisLipid overloadCeramideLipid metabolismInflammasome-dependent mannerOxidative stressDanger signalsFat diet-induced obesityHomeostasisFatty acids
1999
Regulation of myocardial glucose uptake and transport during ischemia and energetic stress
Young L, Russell R, Yin R, Caplan M, Ren J, Bergeron R, Shulman G, Sinusas A. Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. The American Journal Of Cardiology 1999, 83: 25-30. PMID: 10750583, DOI: 10.1016/s0002-9149(99)00253-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEnergetic stressEnergy-generating metabolic pathwaysMonophosphate-activated protein kinaseGlucose uptakeGlucose transport proteinProtein kinaseTransporter translocationTransport proteinsMolecular mechanismsMetabolic pathwaysCardiac glucose uptakeGlucose transporterCellular mechanismsGlucose transportFuel gaugeKinaseTranslocationGlucose entryModerate regional ischemiaSubsequent metabolismGlucose utilization increasesImportant roleUptakeGLUT4Stress