2024
1577-P: CIDEB Knockdown Promotes Increased Hepatic Mitochondrial Fat Oxidation and Reverses Hepatic Steatosis and Hepatic Insulin Resistance by the PKCε-Insulin Receptor Kinase Pathway
ZHENG J, NASIRI A, GASPAR R, HUBBARD B, SAKUMA I, MA X, MURRAY S, PERELIS M, BARNES W, SAMUEL V, PETERSEN K, SHULMAN G. 1577-P: CIDEB Knockdown Promotes Increased Hepatic Mitochondrial Fat Oxidation and Reverses Hepatic Steatosis and Hepatic Insulin Resistance by the PKCε-Insulin Receptor Kinase Pathway. Diabetes 2024, 73 DOI: 10.2337/db24-1577-p.Peer-Reviewed Original ResearchReceptor kinase pathwaysMitochondrial fat oxidationHepatic insulin resistanceKinase pathwayExpression of cidebAmeliorated HFD-induced hepatic steatosisHFD-induced hepatic steatosisHFD-induced insulin resistanceSteatotic liver diseasePathogenesis of type 2 diabetesHepatic steatosisCidebHyperinsulinemic-euglycemic clamp studiesHepatic triglyceride accumulationInsulin resistanceReverse hepatic steatosisTriglyceride accumulationHepatic insulin sensitivityInsulin sensitivityPathwayHepatic expressionHigh-fatWhole-body insulin sensitivityLiver diseaseTranslocation
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
2020
Non‐alcoholic Fatty Liver Disease and Insulin Resistance
Petersen M, Samuel V, Petersen K, Shulman G. Non‐alcoholic Fatty Liver Disease and Insulin Resistance. 2020, 455-471. DOI: 10.1002/9781119436812.ch37.Peer-Reviewed Original ResearchNon-alcoholic fatty liver diseaseHepatic insulin resistanceFatty liver diseaseInsulin resistanceLiver diseaseDevelopment of NAFLDLipid-induced muscle insulin resistanceRandle glucose-fatty acid cycleCommon chronic liver diseaseType 2 diabetes mellitusHyperinsulinemic-euglycemic clamp studiesGlucose-fatty acid cycleLiver-related deathSkeletal muscleChronic liver diseaseNon-alcoholic steatohepatitisMajor risk factorLipid-induced hepatic insulin resistanceMuscle insulin resistanceDiabetes mellitusRisk factorsClamp studiesLipoprotein lipaseDiseaseProtein kinase C
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
2016
Insulin Resistance in Type 2 Diabetes
Roden M, Petersen K, Shulman G. Insulin Resistance in Type 2 Diabetes. 2016, 174-186. DOI: 10.1002/9781118924853.ch13.Peer-Reviewed Original ResearchType 2 diabetesNon-alcoholic fatty liver diseaseInsulin resistanceInflammatory pathwaysAdipose tissueHepatic mitochondrial oxidative capacityLipid-mediated insulin resistanceFatty liver diseaseImpaired glucose toleranceDiabetes-related complicationsEctopic lipid accumulationΒ-cell dysfunctionFatty acid availabilityAction of insulinMitochondrial oxidative capacityAtherogenic dyslipidemiaMultiple deleterious effectsGlucose toleranceLiver diseaseCarbohydrate ingestionEctopic storagePostprandial hyperglycemiaSystemic abnormalitiesInhibits lipolysisFree fatty acids
1994
A liver factor increasing glucose uptake in rat hindquarters
Petersen K, Tygstrup N. A liver factor increasing glucose uptake in rat hindquarters. Journal Of Hepatology 1994, 20: 461-465. PMID: 8051382, DOI: 10.1016/s0168-8278(05)80490-8.Peer-Reviewed Original ResearchConceptsMin-1 xGlucose uptakeRat hindquartersIsolated rat hindquartersIsolated rat liverGlucose intoleranceIsolated perfusionLiver diseaseLiverLiver factorsKidney extractsHindquartersLiver extractsRat liverPerfusionPerfusateTissue extractsBW-1Muscle tissueSecond periodExtract fluidMumolUptakeExtractPeriod