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
2019
Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance
Camporez JP, Lyu K, Goldberg EL, Zhang D, Cline GW, Jurczak MJ, Dixit VD, Petersen KF, Shulman GI. Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance. The Journal Of Physiology 2019, 597: 3885-3903. PMID: 31206703, PMCID: PMC6876753, DOI: 10.1113/jp277270.Peer-Reviewed Original ResearchConceptsObesity-induced insulin resistanceHigh-fat dietEctopic lipid contentWhite adipose tissue lipolysisInsulin resistanceAdipose tissue lipolysisMale miceInsulin sensitivityFemale miceInsulin-stimulated suppressionWAT inflammationTissue lipolysisRodent studiesTumor necrosis factor αWhole-body insulin sensitivityLipid-induced insulin resistanceMetabolic homeostasisAge-matched menInterleukin-6 concentrationsSkeletal muscleAnti-inflammatory effectsType 2 diabetesInsulin-mediated suppressionSexual dimorphic responseNecrosis factor α
2011
Regulation of hepatic fat and glucose oxidation in rats with lipid‐induced hepatic insulin resistance
Alves TC, Befroy DE, Kibbey RG, Kahn M, Codella R, Carvalho RA, Petersen K, Shulman GI. Regulation of hepatic fat and glucose oxidation in rats with lipid‐induced hepatic insulin resistance. Hepatology 2011, 53: 1175-1181. PMID: 21400553, PMCID: PMC3077048, DOI: 10.1002/hep.24170.Peer-Reviewed Original ResearchConceptsLipid-induced hepatic insulin resistanceHepatic insulin resistanceInsulin resistanceTricarboxylic acid fluxFatty acid oxidationPyruvate dehydrogenaseHyperinsulinemic-euglycemic clampHyperinsulinemic-hyperglycemic clampInfusion of somatostatinSubstrate availabilityHigh-fat dietPlasma glucose concentrationRegulationCritical rolePyruvate dehydrogenase fluxHepatic fatHyperglycemic clampAcid oxidationAwake ratsBasal concentrations
2001
Stimulating 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
1999
Contributions 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 subjects
1997
Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis
Petersen K, Jacob R, West A, Sherwin R, Shulman G. Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis. American Journal Of Physiology 1997, 273: e1189-e1193. PMID: 9435535, DOI: 10.1152/ajpendo.1997.273.6.e1189.Peer-Reviewed Original ResearchConceptsMuscle glycogen synthesisInsulin-like growth factor ICirrhotic ratsGrowth factor IGlucose metabolismLiver cirrhosisGlycogen synthesisFactor IInsulin-stimulated muscle glycogen synthesisIGF-I therapyPeripheral glucose metabolismWhole-body glucose turnoverEndogenous glucose productionAbility of IGFEuglycemic clampInsulin resistanceControl ratsAwake ratsCirrhosisDiminished suppressionControl groupIGFRatsGlucose productionGlucose turnover
1995
Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver
Petersen K, Blair J, Shulman G. Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver. Metabolism 1995, 44: 1380-1383. PMID: 7476321, DOI: 10.1016/0026-0495(95)90133-7.Peer-Reviewed Original ResearchConceptsMalic enzymeRelative carbon fluxPyruvate kinaseCarbon fluxesAlanine C2Pyruvate carboxylase fluxSubstrate cyclingKinase activityMalic enzyme activityPyruvate kinase activityPyruvate carboxylaseKinaseEnzymeEnzyme activityCarboxylaseNormal rat liverRat liverNuclear magnetic resonance spectroscopyRelative rolesT3 treatmentOxaloacetateCyclingRecirculating systemPyruvate
1993
Gluconeogenesis in hepatocytes determined with [2-13C] acetate and quantitative 13C NMR spectroscopy
Petersen K, Grunnet N. Gluconeogenesis in hepatocytes determined with [2-13C] acetate and quantitative 13C NMR spectroscopy. The International Journal Of Biochemistry & Cell Biology 1993, 25: 1-5. PMID: 8432377, DOI: 10.1016/0020-711x(93)90482-t.Peer-Reviewed Original Research