Sylvie Dufour
Associate Research Scientist (Endocrinology)Cards
About
Research
Publications
2025
Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive form
2024
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts
Goedeke L, Ma Y, Gaspar R, Nasiri A, Lee J, Zhang D, Galsgaard K, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard B, Haedersdal S, Wu X, Stack J, Dufour S, Butrico G, Kahn M, Perry R, Cline G, Young L, Shulman G. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. Journal Of Clinical Investigation 2024, 134: e176708. PMID: 39680452, PMCID: PMC11645152, DOI: 10.1172/jci176708.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter type 2Heart failureKetone oxidationGas chromatography-mass spectrometryFatty acid oxidationLeft ventricular ejection fractionReduced myocardial oxidative stressVentricular ejection fractionKetone supplementationWeeks of treatmentMyocardial oxidative stressDecreased pyruvate oxidationInduce heart failurePlasma glucose levelsIn vivo effectsSGLT2i treatmentEjection fractionAssociated with improvementsAwake ratsSGLT2 inhibitionCardioprotective benefitsLiquid chromatography-tandem mass spectrometryPlasma ketonesRates of ketonizationChromatography-tandem mass spectrometryGlucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease
Petersen K, Dufour S, Mehal W, Shulman G. Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease. Cell Metabolism 2024, 36: 2359-2366.e3. PMID: 39197461, PMCID: PMC11612994, DOI: 10.1016/j.cmet.2024.07.023.Peer-Reviewed Original Research
2023
Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH
Insogna K, Sullivan R, Parziale S, Deng Y, Carrano D, Simpson C, Dufour S, Carpenter T, Petersen K. Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH. The Journal Of Clinical Endocrinology & Metabolism 2023, 109: e1061-e1071. PMID: 37930769, DOI: 10.1210/clinem/dgad642.Peer-Reviewed Original ResearchSymptoms of painMuscle function testsFunction testsMuscle strengthMuscle functionSkeletal muscleLower extremity joint painSTS testMuscle function studiesImproved muscle functionTreatment-naïve adultsSynthesis rateMonths of studyJoint painThird doseSymptomatic adultsClinical trialsRight calfATP synthesis rateBurosumabPainMuscle concentrationsXLHSymptomsMuscleThe 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
AS018 Carbohydrate restriction reverses NAFLD by altering hepatic mitochondrial fluxes in humans
Luukkonen P, Dufour S, Lyu K, Zhang X, Hakkarainen A, Lehtimäki T, Cline G, Petersen K, Shulman G, Yki-Järvinen H. AS018 Carbohydrate restriction reverses NAFLD by altering hepatic mitochondrial fluxes in humans. Journal Of Hepatology 2020, 73: s14. DOI: 10.1016/s0168-8278(20)30588-2.Peer-Reviewed Original Research
2019
19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates
GOEDEKE L, ROMERAL V, BUTRICO G, KAHN M, DUFOUR S, ZHANG X, CLINE G, PETERSEN K, CHNG K, SHULMAN G. 19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates. Diabetes 2019, 68 DOI: 10.2337/db19-19-or.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreSpouse/partnerCRMP treatmentInsulin resistanceDiet-induced rodent modelJanssen ResearchReversal of hypertriglyceridemiaNAFLD/NASHInflammation/fibrosisNonhuman primate modelMitochondrial protonophoreEndogenous glucose productionHepatic insulin resistanceHepatic acetyl-CoA contentAdvisory PanelMitochondrial fat oxidationMetabolic syndromeFatty liverHepatic steatosisAdverse reactionsHepatic triglyceridesAcetyl-CoA contentPrimate modelNovo Nordisk A/S.Food intake225-OR: Key Role for Glucose-Alanine Cycling in the Regulation of Hepatic Mitochondrial Oxidation during Starvation in Humans
PETERSEN K, DUFOUR S, CLINE G, SHULMAN G. 225-OR: Key Role for Glucose-Alanine Cycling in the Regulation of Hepatic Mitochondrial Oxidation during Starvation in Humans. Diabetes 2019, 68 DOI: 10.2337/db19-225-or.Peer-Reviewed Original Research
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
News
News
- February 18, 2025
What Makes a Successful Heart Failure Drug Work?
- April 14, 2022
Small Amounts of Liver Fat Lead to Insulin Resistance and Increased Cardiometabolic Risk Factors
- November 08, 2017
Study reveals how a very low calorie diet can reverse type 2 diabetes
- August 25, 2005
Rate of Cellular Energy Production Lower in Persons at Risk for Type 2 Diabetes