2023
The 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 functionInhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis
Luukkonen P, Sakuma I, Gaspar R, Mooring M, Nasiri A, Kahn M, Zhang X, Zhang D, Sammalkorpi H, Penttilä A, Orho-Melander M, Arola J, Juuti A, Zhang X, Yimlamai D, Yki-Järvinen H, Petersen K, Shulman G. Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2217543120. PMID: 36669104, PMCID: PMC9942818, DOI: 10.1073/pnas.2217543120.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseLiver fibrosisLiver diseaseCommon chronic liver diseaseChronic liver diseaseFatty liver diseaseRisk of fibrosisDistinct mouse modelsPyrimidine catabolismNonalcoholic steatohepatitisMouse modelTherapeutic targetFibrosisDihydropyrimidine dehydrogenaseHuman liverA variantCommon variantsMetabolomics approachDiseaseMiceInhibitionCatabolismKnockdownSteatohepatitisGimeracil
2009
Chapter 21 Assessment of In Vivo Mitochondrial Metabolism by Magnetic Resonance Spectroscopy
Befroy DE, Petersen K, Rothman DL, Shulman GI. Chapter 21 Assessment of In Vivo Mitochondrial Metabolism by Magnetic Resonance Spectroscopy. Methods In Enzymology 2009, 457: 373-393. PMID: 19426879, PMCID: PMC3077057, DOI: 10.1016/s0076-6879(09)05021-6.Peer-Reviewed Original Research
2007
The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
Petersen KF, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, Cline GW, Befroy D, Zemany L, Kahn BB, Papademetris X, Rothman DL, Shulman GI. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 12587-12594. PMID: 17640906, PMCID: PMC1924794, DOI: 10.1073/pnas.0705408104.Peer-Reviewed Original ResearchConceptsPlasma high-density lipoprotein concentrationsHigh-density lipoprotein concentrationsHepatic de novo lipogenesisMuscle glycogen synthesisInsulin resistanceInsulin-resistant subjectsPlasma triglyceride concentrationsDe novo lipogenesisMetabolic syndromeAtherogenic dyslipidemiaIL-6Lipoprotein concentrationsTNF-alphaPlasma concentrationsTriglyceride concentrationsNovo lipogenesisGlycogen synthesisIntraabdominal fat volumeSkeletal muscle insulin resistanceSkeletal muscleProtein 4Skeletal muscle glycogen synthesisMuscle insulin resistanceHepatic triglyceride synthesisIntraabdominal obesity
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 ResearchStimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans
Petersen K, Laurent D, Yu C, Cline G, Shulman G. Stimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans. Diabetes 2001, 50: 1263-1268. PMID: 11375325, DOI: 10.2337/diabetes.50.6.1263.Peer-Reviewed Original ResearchConceptsNet hepatic glycogen synthesisHepatic glycogen synthesisGlycogen synthesisSynthase fluxInfusion of fructoseLow-dose infusionType 2 diabetesEuglycemic hyperinsulinemic conditionsPotential therapeutic valueHepatic glycogen metabolismThreefold increaseFructose studiesEuglycemic hyperinsulinemiaHyperinsulinemic conditionsFructose infusionControl studyTherapeutic valueInfusionType 1Glucokinase activityGlycogen metabolismIndirect pathwaysStimulating effectInsulinStimulationContribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humans
Petersen K, Cline G, Gerard D, Magnusson I, Rothman D, Shulman G. Contribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humans. Metabolism 2001, 50: 598-601. PMID: 11319724, DOI: 10.1053/meta.2001.22561.Peer-Reviewed Original ResearchConceptsHepatic glycogen synthesisOral glucose loadGlucose loadMagnetic resonance imagingLiver glycogen synthesisNet hepatic glycogen synthesisLiver volumeGlycogen synthesisWhole-body glucose disposalGlycogen contentHepatic glycogen concentrationIngestion of glucoseLiver glycogen contentHepatic glycogen contentIdentical glucose loadHepatic UDP-glucoseGlucose disposalGroup 2Group 1Direct pathwayResonance imagingGlycogen concentrationMean maximum rateLiverIngestion
2000
Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during Exercise1
Laurent D, Schneider K, Prusaczyk W, Franklin C, Vogel S, Krssak M, Petersen K, Goforth H, Shulman G. Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during Exercise1. The Journal Of Clinical Endocrinology & Metabolism 2000, 85: 2170-2175. PMID: 10852448, DOI: 10.1210/jcem.85.6.6655.Peer-Reviewed Original ResearchConceptsMuscle glycogen contentMuscle glycogen utilizationGlycogen contentCaffeine ingestionNeuroendocrine axisGlycogen utilizationGlycogen-sparing effectFree fatty acid concentrationsBeta-endorphin levelsCaffeine-treated groupExercise-induced glycogen depletionMaximal oxygen consumptionEffects of caffeineHigher muscle glycogen contentPlacebo groupExercise enduranceFatty acid concentrationsPlasma concentrationsNeuroendocrine hormonesCortisol releaseProlonged exerciseGlycogen depletionPlasma lactateNormal valuesThigh musclesMechanism of muscle glycogen autoregulation in humans
Laurent D, Hundal R, Dresner A, Price T, Vogel S, Petersen K, Shulman G. Mechanism of muscle glycogen autoregulation in humans. AJP Endocrinology And Metabolism 2000, 278: e663-e668. PMID: 10751200, DOI: 10.1152/ajpendo.2000.278.4.e663.Peer-Reviewed Original ResearchConceptsInsulin-stimulated ratesWhole body glucose oxidation ratesMuscle glycogenGlycogen loadingPlasma free fatty acid concentrationsWhole-body glucose uptakeFree fatty acid concentrationsMuscle glycogen contentGlucose oxidation ratesMuscle glycogen synthesisPlasma lactate concentrationTwofold increaseHyperinsulinemic clampGlycogen synthase activityFatty acid concentrationsLoading protocolGlucose infusionHealthy volunteersLactate concentrationGlycogen contentGlucose uptakeAnaerobic glycolysisGlycogen synthesisUnlabeled glucose infusionGlycogenGlycogen loading alters muscle glycogen resynthesis after exercise
Price T, Laurent D, Petersen K, Rothman D, Shulman G. Glycogen loading alters muscle glycogen resynthesis after exercise. Journal Of Applied Physiology 2000, 88: 698-704. PMID: 10658040, DOI: 10.1152/jappl.2000.88.2.698.Peer-Reviewed Original ResearchConceptsMaximum voluntary contractionGlycogen recoveryNOR trialMuscle glycogen resynthesisMuscle glycogen recoveryNormal resting levelsGlycogen resynthesisVoluntary contractionHeavy exercisePlantar flexionResting levelGlycogen concentrationGlycogen levelsSeparate occasionsSimilar glucoseUntrained subjectsTrialsGlycogen synthesisExerciseExtended recoverySubjectsRecoveryLevelsMinFlexion
1999
Impaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 Diabetes
Cline G, Petersen K, Krssak M, Shen J, Hundal R, Trajanoski Z, Inzucchi S, Dresner A, Rothman D, Shulman G. Impaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 Diabetes. New England Journal Of Medicine 1999, 341: 240-246. PMID: 10413736, DOI: 10.1056/nejm199907223410404.Peer-Reviewed Original ResearchConceptsMuscle glycogen synthesisType 2 diabetes mellitusConcentrations of insulinNormal subjectsDiabetes mellitusGlucose metabolismGlycogen synthesisGlucose concentrationWhole-body glucose metabolismInsulin-stimulated muscle glycogen synthesisIntracellular glucose concentrationType 2 diabetesPlasma insulin concentrationGlucose transportImpaired glucose transportInterstitial fluid glucose concentrationsOpen-flow microperfusionIntramuscular glucoseInterstitial fluidGlucose-6-phosphate concentrationInsulin resistanceVivo microdialysisInsulin concentrationsHyperinsulinemic conditionsPatientsDetermination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR
Shen J, Petersen K, Behar K, Brown P, Nixon T, Mason G, Petroff O, Shulman G, Shulman R, Rothman D. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8235-8240. PMID: 10393978, PMCID: PMC22218, DOI: 10.1073/pnas.96.14.8235.Peer-Reviewed Original ResearchConceptsGlutamate/glutamine cycleGlutamine cycleCerebral cortexMin/Rat cerebral cortexVivo 13C NMR spectraGlucose oxidation ratesHuman brainGlucose oxidationGlutamatergic activityRat modelTricarboxylic acid cycle rateParietal lobeHuman cortexCortexTime courseBrainGlutamine synthesisMajor metabolic fluxCycle rateTricarboxylic acid cycleHigh levelsInfusionRatsAcid cycleContributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis
Petersen K, Krssak M, Navarro V, Chandramouli V, Hundal R, Schumann W, Landau B, Shulman G. Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis. American Journal Of Physiology 1999, 276: e529-e535. PMID: 10070020, DOI: 10.1152/ajpendo.1999.276.3.e529.Peer-Reviewed Original ResearchConceptsNet hepatic glycogenolysisCirrhotic subjectsHepatic glycogenolysisControl subjectsGlucose productionFree insulin-like growth factor IInsulin-like growth factor IHepatic glycogen concentrationGrowth factor IHepatic glycogen contentMagnetic resonance imagingRate of gluconeogenesisBlood glucosePlasma levelsHealthy subjectsEffects 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
1998
Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans
Laurent D, Petersen K, Russell R, Cline G, Shulman G. Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans. American Journal Of Physiology 1998, 274: e130-e138. PMID: 9458758, DOI: 10.1152/ajpendo.1998.274.1.e130.Peer-Reviewed Original ResearchConceptsInsulin-stimulated muscle glycogen synthesisMuscle glycogen synthesisMuscle glycogenolysisEpinephrine infusionPhysiological increaseWhole-body glucose oxidationMuscle glycogen synthesis ratesPlasma epinephrine concentrationEuglycemic hyperinsulinemic clampGlucose infusion rateEffect of epinephrineGlycogen synthesisInsulin-stimulated glycogenesisBasal insulinControl subjectsPlasma glucoseEpinephrine concentrationsFree fatty acidsBasal valuesInfusion rateGlycogen synthesis rateMuscle glycogenEpinephrineGlycogenolysisMajor impairment
1997
New insulins and other possible therapeutic approaches
Johannesen J, Petersen K, Berger M, Binder C. New insulins and other possible therapeutic approaches. Diabetologia 1997, 40: b89. PMID: 9345654, DOI: 10.1007/bf03168195.Peer-Reviewed Original Research