2024
Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease
Petersen K, Dufour S, Mehal W, Shulman G. Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease. Cell Metabolism 2024 PMID: 39197461, DOI: 10.1016/j.cmet.2024.07.023.Peer-Reviewed Original Research
2023
Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH
Insogna K, Sullivan R, Parziale S, Deng Y, Carrano D, Simpson C, Dufour S, Carpenter T, Petersen K. Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH. The Journal Of Clinical Endocrinology & Metabolism 2023, 109: e1061-e1071. PMID: 37930769, DOI: 10.1210/clinem/dgad642.Peer-Reviewed Original ResearchSymptoms of painMuscle function testsFunction testsMuscle strengthMuscle functionSkeletal muscleLower extremity joint painSTS testMuscle function studiesImproved muscle functionTreatment-naïve adultsSynthesis rateMonths of studyJoint painThird doseSymptomatic adultsClinical trialsRight calfATP synthesis rateBurosumabPainMuscle concentrationsXLHSymptomsMuscleThe PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
Luukkonen P, Porthan K, Ahlholm N, Rosqvist F, Dufour S, Zhang X, Lehtimäki T, Seppänen W, Orho-Melander M, Hodson L, Petersen K, Shulman G, Yki-Järvinen H. The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans. Cell Metabolism 2023, 35: 1887-1896.e5. PMID: 37909034, DOI: 10.1016/j.cmet.2023.10.008.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisHepatic de novo lipogenesisPlasma β-hydroxybutyrate concentrationsΒ-hydroxybutyrate concentrationsLiver diseaseNovo lipogenesisPNPLA3 I148M variantHepatic mitochondrial redox stateMajor genetic risk factorI148M variantFatty liver diseaseGenetic risk factorsHepatic mitochondrial dysfunctionKetogenic dietMixed mealRisk factorsHepatic metabolismHomozygous carriersM carriersMitochondrial dysfunctionCitrate synthase fluxM variantKetogenesisMitochondrial redox stateMitochondrial function
2022
SAT052 The PNPLA3 I148M variant increases intrahepatic lipolysis and beta oxidation and decreases de novo lipogenesis and hepatic mitochondrial function in humans
Luukkonen P, Porthan K, Ahlholm N, Rosqvist F, Dufour S, Zhang X, Dabek J, Lehtimäki T, Seppänen W, Orho-Melander M, Hodson L, Petersen K, Shulman G, Yki-Järvinen H. SAT052 The PNPLA3 I148M variant increases intrahepatic lipolysis and beta oxidation and decreases de novo lipogenesis and hepatic mitochondrial function in humans. Journal Of Hepatology 2022, 77: s690-s691. DOI: 10.1016/s0168-8278(22)01698-1.Peer-Reviewed Original Research
2020
AS018 Carbohydrate restriction reverses NAFLD by altering hepatic mitochondrial fluxes in humans
Luukkonen P, Dufour S, Lyu K, Zhang X, Hakkarainen A, Lehtimäki T, Cline G, Petersen K, Shulman G, Yki-Järvinen H. AS018 Carbohydrate restriction reverses NAFLD by altering hepatic mitochondrial fluxes in humans. Journal Of Hepatology 2020, 73: s14. DOI: 10.1016/s0168-8278(20)30588-2.Peer-Reviewed Original Research
2019
225-OR: Key Role for Glucose-Alanine Cycling in the Regulation of Hepatic Mitochondrial Oxidation during Starvation in Humans
PETERSEN K, DUFOUR S, CLINE G, SHULMAN G. 225-OR: Key Role for Glucose-Alanine Cycling in the Regulation of Hepatic Mitochondrial Oxidation during Starvation in Humans. Diabetes 2019, 68 DOI: 10.2337/db19-225-or.Peer-Reviewed Original Research19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates
GOEDEKE L, ROMERAL V, BUTRICO G, KAHN M, DUFOUR S, ZHANG X, CLINE G, PETERSEN K, CHNG K, SHULMAN G. 19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates. Diabetes 2019, 68 DOI: 10.2337/db19-19-or.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreSpouse/partnerCRMP treatmentInsulin resistanceDiet-induced rodent modelJanssen ResearchReversal of hypertriglyceridemiaNAFLD/NASHInflammation/fibrosisNonhuman primate modelMitochondrial protonophoreEndogenous glucose productionHepatic insulin resistanceHepatic acetyl-CoA contentAdvisory PanelMitochondrial fat oxidationMetabolic syndromeFatty liverHepatic steatosisAdverse reactionsHepatic triglyceridesAcetyl-CoA contentPrimate modelNovo Nordisk A/S.Food intake
2018
Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis
PERRY R, WANG Y, BRILL A, PENG L, ZHANG D, DUFOUR S, ZHANG Y, ZHANG X, NOZAKI Y, CLINE G, EHRLICH B, PETERSEN K, SHULMAN G. Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis. Diabetes 2018, 67 DOI: 10.2337/db18-146-or.Peer-Reviewed Original ResearchSpouse/partnerHigh-fat diet-induced hepatic steatosisNonalcoholic fatty liver diseaseDiet-induced hepatic steatosisGilead SciencesFatty liver diseasePlasma glucagon concentrationsType 2 diabetesHepatic acetyl-CoA contentLiver-specific knockdownIntracellular calcium signalingMitochondrial oxidationGlucose intoleranceAdipocyte triglyceride lipaseLiver diseaseWT miceGlucagon concentrationsHepatic steatosisGlucagon infusionAcetyl-CoA contentChronic increaseHepatic mitochondrial oxidationGlucagon biologyGlucagon stimulationKnockout mice
2012
Skeletal Muscle Insulin Resistance Promotes Increased Hepatic De Novo Lipogenesis, Hyperlipidemia, and Hepatic Steatosis in the Elderly
Flannery C, Dufour S, Rabøl R, Shulman GI, Petersen KF. Skeletal Muscle Insulin Resistance Promotes Increased Hepatic De Novo Lipogenesis, Hyperlipidemia, and Hepatic Steatosis in the Elderly. Diabetes 2012, 61: 2711-2717. PMID: 22829450, PMCID: PMC3478531, DOI: 10.2337/db12-0206.Peer-Reviewed Original ResearchConceptsHepatic de novo lipogenesisNonalcoholic fatty liver diseaseDe novo lipogenesisMuscle insulin resistanceInsulin resistanceElderly subjectsNovo lipogenesisYoung subjectsInsulin resistance promotesSedentary elderly subjectsFatty liver diseaseHigh-carbohydrate mealHepatic triglyceride contentType 2 diabetesMuscle glycogen synthesisGlycogen synthesisLiver glycogen synthesisLiver diseaseNormal weightHepatic steatosisPostprandial changesPlasma TGLiver glycogenHyperlipidemiaMuscle glycogenReversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes
Petersen KF, Dufour S, Morino K, Yoo PS, Cline GW, Shulman GI. Reversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 8236-8240. PMID: 22547801, PMCID: PMC3361376, DOI: 10.1073/pnas.1205675109.Peer-Reviewed Original ResearchConceptsMuscle insulin resistanceInsulin-resistant offspringType 2 diabetesBranched-chain amino acidsInsulin resistanceIR offspringInsulin-stimulated muscle glucose uptakeWeight lossPeripheral insulin responsivenessReduction of IMCLModest weight lossPeripheral glucose metabolismC-reactive proteinHyperinsulinemic-euglycemic clampIntramyocellular lipid accumulationMuscle glucose uptakeAverage weight lossWeight reductionTotal adiponectinHypocaloric dietIL-6IMCL contentPlasma concentrationsWeight stabilizationIMCL accumulation
2011
Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals
Rabøl R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 13705-13709. PMID: 21808028, PMCID: PMC3158147, DOI: 10.1073/pnas.1110105108.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseHepatic de novo lipogenesisMuscle insulin resistanceInsulin-resistant individualsDe novo lipogenesisSkeletal muscle insulin resistanceCarbohydrate-rich mealInsulin resistanceHepatic triglyceride synthesisNovo lipogenesisAtherogenic dyslipidemiaMetabolic syndromeRandomized cross-over trialTriglyceride synthesisFatty liver diseasePostprandial plasma glucoseMuscle insulin responsivenessCross-over trialEarly therapeutic targetType 2 diabetesMuscle glycogen synthesisBody energy storageLiver diseasePlasma glucoseSingle bout
2004
Impaired Mitochondrial Activity in Insulin resistant offspring of Type 2 Diabetics
Petersen K, Dufour S, Befroy D, Garcia R, Shulman G. Impaired Mitochondrial Activity in Insulin resistant offspring of Type 2 Diabetics. Journal Of Investigative Medicine 2004, 52: 381-381. DOI: 10.1177/108155890405202s100.Peer-Reviewed Original Research26 IMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS.
Petersen K, Dufour S, Befroy D, Garcia R, Shulman G. 26 IMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS. Journal Of Investigative Medicine 2004, 52: s381. DOI: 10.1136/jim-52-suppl2-100.Peer-Reviewed Original ResearchIMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS.: 26
Petersen K, Dufour S, Befroy D, Garcia R, Shulman G. IMPAIRED MITOCHONDRIAL ACTIVITY IN INSULIN RESISTANT OFFSPRING OF TYPE 2 DIABETICS.: 26. Journal Of Investigative Medicine 2004, 52: s381. DOI: 10.1097/00042871-200403002-00100.Peer-Reviewed Original Research
2003
Alterata attività mitocondriale nella prole insulino-resistente di pazienti con diabete di tipo 2
Petersen K, Dufour S, Befroy D, Garcia R, Shulman G, Pezzino V. Alterata attività mitocondriale nella prole insulino-resistente di pazienti con diabete di tipo 2. L'Endocrinologo 2003, 4: 224-225. DOI: 10.1007/bf03344480.Peer-Reviewed Original Research
2001
Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle
Lebon V, Dufour S, Petersen K, Ren J, Jucker B, Slezak L, Cline G, Rothman D, Shulman G. Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. Journal Of Clinical Investigation 2001, 108: 733-737. PMID: 11544279, PMCID: PMC209375, DOI: 10.1172/jci11775.Peer-Reviewed Original ResearchIn Vivo Effects of Uncoupling Protein-3 Gene Disruption on Mitochondrial Energy Metabolism*
Cline G, Vidal-Puig A, Dufour S, Cadman K, Lowell B, Shulman G. In Vivo Effects of Uncoupling Protein-3 Gene Disruption on Mitochondrial Energy Metabolism*. Journal Of Biological Chemistry 2001, 276: 20240-20244. PMID: 11274222, DOI: 10.1074/jbc.m102540200.Peer-Reviewed Original ResearchConceptsATP synthesisEnergy metabolismSkeletal muscleMitochondrial oxidative phosphorylationMitochondrial energy metabolismGene disruptionRatio of ATPOxidative phosphorylationATP productionTricarboxylic acid cycle fluxWhole-body levelUCP3KO miceWhole-body energy expenditureCellular levelProtein 3Cycle fluxLabeling experimentsFirst evidenceBody energy expenditureMetabolismVivoMeasurement of ratesPhosphorylationEnergy expenditureUCP3
2000
13C/31P NMR Assessment of Mitochondrial Energy Coupling in Skeletal Muscle of Awake Fed and Fasted Rats RELATIONSHIP WITH UNCOUPLING PROTEIN 3 EXPRESSION*
Jucker B, Ren J, Dufour S, Cao X, Previs S, Cadman K, Shulman G. 13C/31P NMR Assessment of Mitochondrial Energy Coupling in Skeletal Muscle of Awake Fed and Fasted Rats RELATIONSHIP WITH UNCOUPLING PROTEIN 3 EXPRESSION*. Journal Of Biological Chemistry 2000, 275: 39279-39286. PMID: 10995775, DOI: 10.1074/jbc.m007760200.Peer-Reviewed Original ResearchAdenosine TriphosphateAlbuminsAnimalsBlotting, NorthernBlotting, WesternCarnitine O-PalmitoyltransferaseCarrier ProteinsEnzyme InhibitorsEpoxy CompoundsFatty AcidsFood DeprivationGlutamic AcidIon ChannelsKineticsMagnetic Resonance SpectroscopyMitochondriaMitochondrial ProteinsModels, BiologicalModels, ChemicalMuscle, SkeletalOxygenPalmitatesRatsRats, Sprague-DawleyRNA, MessengerTime FactorsTricarboxylic AcidsUncoupling Protein 3Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR
Jucker B, Dufour S, Ren J, Cao X, Previs S, Underhill B, Cadman K, Shulman G. Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 6880-6884. PMID: 10823916, PMCID: PMC18769, DOI: 10.1073/pnas.120131997.Peer-Reviewed Original Research
1999
Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
Dresner A, Laurent D, Marcucci M, Griffin M, Dufour S, Cline G, Slezak L, Andersen D, Hundal R, Rothman D, Petersen K, Shulman G. Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity. Journal Of Clinical Investigation 1999, 103: 253-259. PMID: 9916137, PMCID: PMC407880, DOI: 10.1172/jci5001.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultFatty Acids, NonesterifiedFemaleGlucoseGlucose Clamp TechniqueGlucose-6-PhosphateGlycerolGlycogenHumansHyperinsulinismInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipid MetabolismMagnetic Resonance SpectroscopyMaleMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsConceptsFree fatty acidsIRS-1-associated phosphatidylinositolLipid infusionInsulin resistanceGlycerol infusionPlasma free fatty acidsWhole-body glucose uptakeFive-hour infusionLipid/heparinHyperinsulinemic-euglycemic clampGlucose concentrationGlucose transportMuscle glycogen synthesisDiminished glucose transportMuscle biopsy samplesHuman skeletal muscleRate of insulinGlucose-6-phosphate concentrationFatty acidsHealthy subjectsBiopsy samplesInfusion studiesIdentical protocolInfusionIRS-1-associated PI