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
2012
Skeletal Muscle Insulin Resistance Promotes Increased Hepatic De Novo Lipogenesis, Hyperlipidemia, and Hepatic Steatosis in the Elderly
Flannery C, Dufour S, Rabøl R, Shulman GI, Petersen KF. Skeletal Muscle Insulin Resistance Promotes Increased Hepatic De Novo Lipogenesis, Hyperlipidemia, and Hepatic Steatosis in the Elderly. Diabetes 2012, 61: 2711-2717. PMID: 22829450, PMCID: PMC3478531, DOI: 10.2337/db12-0206.Peer-Reviewed Original ResearchConceptsHepatic de novo lipogenesisNonalcoholic fatty liver diseaseDe novo lipogenesisMuscle insulin resistanceInsulin resistanceElderly subjectsNovo lipogenesisYoung subjectsInsulin resistance promotesSedentary elderly subjectsFatty liver diseaseHigh-carbohydrate mealHepatic triglyceride contentType 2 diabetesMuscle glycogen synthesisGlycogen synthesisLiver glycogen synthesisLiver diseaseNormal weightHepatic steatosisPostprandial changesPlasma TGLiver glycogenHyperlipidemiaMuscle glycogen
2011
Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals
Rabøl R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 13705-13709. PMID: 21808028, PMCID: PMC3158147, DOI: 10.1073/pnas.1110105108.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseHepatic de novo lipogenesisMuscle insulin resistanceInsulin-resistant individualsDe novo lipogenesisSkeletal muscle insulin resistanceCarbohydrate-rich mealInsulin resistanceHepatic triglyceride synthesisNovo lipogenesisAtherogenic dyslipidemiaMetabolic syndromeRandomized cross-over trialTriglyceride synthesisFatty liver diseasePostprandial plasma glucoseMuscle insulin responsivenessCross-over trialEarly therapeutic targetType 2 diabetesMuscle glycogen synthesisBody energy storageLiver diseasePlasma glucoseSingle bout