2023
Inhibition 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
2022
Bioactive lipids and metabolic syndrome—a symposium report
DeVito LM, Dennis EA, Kahn BB, Shulman GI, Witztum JL, Sadhu S, Nickels J, Spite M, Smyth S, Spiegel S. Bioactive lipids and metabolic syndrome—a symposium report. Annals Of The New York Academy Of Sciences 2022, 1511: 87-106. PMID: 35218041, PMCID: PMC9219555, DOI: 10.1111/nyas.14752.Peer-Reviewed Original ResearchConceptsBioactive lipidsMetabolic syndromeCardiometabolic conditionsCardiovascular diseaseAnimal modelsDietary lipidsLipid metabolismMetabolic homeostasisMultitude of functionsLipidomic approachLipid pathwaysContinued investigationSyndromeMolecular functionsSymposium reportGenetic studiesLipidsPathwayInflammationGreater understandingDiseaseLiverMacrophagesLipogenesis
2021
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 2021, 184: 2537-2564. PMID: 33989548, DOI: 10.1016/j.cell.2021.04.015.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseProgressive liver injuryFatty liver diseaseNonalcoholic steatohepatitisLiver diseaseLiver injuryHepatocellular carcinomaEffect of NAFLDHepatic stellate cell activationChronic liver diseaseBile acid toxicityStellate cell activationFibrosis progressionAdvanced subtypesMacrophage dysfunctionPathogenetic mechanismsCell activationHepatic glucoseLipid metabolismDisease consequencesDiseaseAcid toxicityCarcinomaInjuryMetabolic originTherapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH
Goedeke L, Shulman GI. Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH. Molecular Metabolism 2021, 46: 101178. PMID: 33545391, PMCID: PMC8085597, DOI: 10.1016/j.molmet.2021.101178.Peer-Reviewed Original ResearchConceptsFatty liver diseaseLiver diseaseSmall molecule mitochondrial uncouplersTherapeutic potentialMitochondrial uncouplerNon-human primate studiesType 2 diabetesWide therapeutic indexSystemic toxicity concernsTreatment of MetabolicCell-specific effectsInsulin resistanceTherapeutic indexMetabolic diseasesNonalcoholic hepatosteatosisSustained increaseToxicity concernsPrimate studiesDiseaseTherapeutic developmentMitochondrial inefficiencyNutrient oxidationATP productionTreatmentTissue
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
2019
Nonalcoholic Fatty Liver Disease, Insulin Resistance, and Ceramides
Samuel VT, Shulman GI. Nonalcoholic Fatty Liver Disease, Insulin Resistance, and Ceramides. New England Journal Of Medicine 2019, 381: 1866-1869. PMID: 31693811, DOI: 10.1056/nejmcibr1910023.Peer-Reviewed Original Research
2014
The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes
Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 2014, 510: 84-91. PMID: 24899308, PMCID: PMC4489847, DOI: 10.1038/nature13478.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsType 2 diabetesHepatic insulin resistanceNon-alcoholic fatty liver diseaseFatty liver diseaseInsulin resistanceLiver diseaseHepatic lipidsHealth care costsInflammatory signalingTherapeutic approachesMortality rateDiabetesRelated epidemicsProtein kinase CεDiseaseCellular modificationsEpidemicLipid speciesMorbidityLipidsDiacylglycerol activationMice