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 function
2020
Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease
Luukkonen PK, Dufour S, Lyu K, Zhang XM, Hakkarainen A, Lehtimäki TE, Cline GW, Petersen KF, Shulman GI, Yki-Järvinen H. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 7347-7354. PMID: 32179679, PMCID: PMC7132133, DOI: 10.1073/pnas.1922344117.Peer-Reviewed Original ResearchMeSH KeywordsBody CompositionCitrate (si)-SynthaseDiet, KetogenicFatty AcidsFatty Acids, NonesterifiedFatty LiverFemaleHumansInsulinInsulin ResistanceLipoproteins, VLDLLiverMaleMiddle AgedMitochondriaNon-alcoholic Fatty Liver DiseaseObesityOverweightOxidation-ReductionPyruvate CarboxylaseTriglyceridesConceptsNonalcoholic fatty liver diseaseFatty liver diseaseIntrahepatic triglyceridesKetogenic dietHepatic insulin resistanceNonesterified fatty acidsInsulin resistanceLiver diseaseOverweight/obese subjectsHepatic mitochondrial redox stateSerum insulin concentrationsHepatic mitochondrial metabolismProton magnetic resonance spectroscopyStable isotope infusionKD dietObese subjectsFatty acidsPlasma leptinHepatic steatosisInsulin concentrationsNEFA concentrationsBody weightTriiodothyronine concentrationsIsotope infusionWeight loss