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
2022
SAT052 The PNPLA3 I148M variant increases intrahepatic lipolysis and beta oxidation and decreases de novo lipogenesis and hepatic mitochondrial function in humans
Luukkonen P, Porthan K, Ahlholm N, Rosqvist F, Dufour S, Zhang X, Dabek J, Lehtimäki T, Seppänen W, Orho-Melander M, Hodson L, Petersen K, Shulman G, Yki-Järvinen H. SAT052 The PNPLA3 I148M variant increases intrahepatic lipolysis and beta oxidation and decreases de novo lipogenesis and hepatic mitochondrial function in humans. Journal Of Hepatology 2022, 77: s690-s691. DOI: 10.1016/s0168-8278(22)01698-1.Peer-Reviewed Original Research
2020
One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension
Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, Jorgensen JA, Schaart G, Zhang D, Meijer K, Hopman M, Hesselink MKC, Ouwens DM, Shulman GI, Schrauwen-Hinderling VB, Schrauwen P. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia 2020, 63: 1211-1222. PMID: 32185462, PMCID: PMC7228997, DOI: 10.1007/s00125-020-05128-1.Peer-Reviewed Original ResearchConceptsMitochondrial oxidative capacityLow mitochondrial oxidative capacityLipid infusionInsulin resistancePhysical inactivityOxidative capacityLipid-induced insulin resistanceUnilateral lower limb suspensionConclusions/interpretationTogetherIntramyocellular lipid depositionMusculus tibialis anteriorChronic metabolic disorderIntramyocellular lipid accumulationType 2 diabetesReduced insulin sensitivityMuscle fat accumulationMusculus vastus lateralisMitochondrial functionUnilateral limb suspensionIMCL contentContralateral legInsulin sensitivityResultsIn vivoTibialis anteriorFat accumulationMitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications
Sangwung P, Petersen KF, Shulman GI, Knowles JW. Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications. Endocrinology 2020, 161: bqaa017. PMID: 32060542, PMCID: PMC7341556, DOI: 10.1210/endocr/bqaa017.Peer-Reviewed Original ResearchConceptsInsulin resistanceWhole-body insulin resistanceMitochondrial functionEctopic lipid depositionBody insulin resistanceType 2 diabetesWhite adipose tissuePrediabetic individualsVivo metabolic studiesInsulin-responsive tissuesLipid depositionAdipose tissueType 2Skeletal muscleMitochondrial dysfunctionPotential mechanismsMetabolic studiesHuman genetic studiesTissueEnvironmental determinantsMitochondrial malfunctionCellular energy balanceRecent insightsCritical roleDiabetes