2024
Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease
Gaspar R, Sakuma I, Nasiri A, Hubbard B, LaMoia T, Leitner B, Tep S, Xi Y, Green E, Ullman J, Petersen K, Shulman G. Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease. AJP Endocrinology And Metabolism 2024, 327: e524-e532. PMID: 39171753, PMCID: PMC11482269, DOI: 10.1152/ajpendo.00175.2024.Peer-Reviewed Original ResearchGAA-KO miceMouse model of Pompe diseaseModel of Pompe diseasePompe diseaseMetabolic dysregulationRegular chowMouse modelSmall molecule inhibitionInsulin sensitivityReduced spontaneous activityGroups of male miceEnzyme acid alpha-glucosidaseProgressive muscle weaknessImprove metabolic dysregulationSynthase IWhole-body insulin sensitivityAcid alpha-glucosidaseImproved glucose toleranceIncreased AMPK phosphorylationWT miceAbnormal accumulation of glycogenGlycogen storage disorderMale miceSpontaneous activityImproved biomarkers292-OR: Coenzyme A Synthase Knockdown Alleviates Metabolic Dysfunction–Associated Steatohepatitis via Decreasing Cholesterol in Liver Lipid Droplets
SAKUMA I, GASPAR R, NASIRI A, KAHN M, GUERRA M, YIMLAMAI D, MURRAY S, PERELIS M, BARNES W, VATNER D, PETERSEN K, SAMUEL V, SHULMAN G. 292-OR: Coenzyme A Synthase Knockdown Alleviates Metabolic Dysfunction–Associated Steatohepatitis via Decreasing Cholesterol in Liver Lipid Droplets. Diabetes 2024, 73 DOI: 10.2337/db24-292-or.Peer-Reviewed Original ResearchCholine-deficient l-amino acid-defined high-fat dietAccumulation of cholesterolMRNA expressionPlasma ALTL-amino acid-defined high-fat dietProtective effectLiver lipid dropletsType 2 diabetesPotential therapeutic approachHigh-fat dietDecreased plasma ALTFibrosis markersFree cholesterol accumulationLipid dropletsLiver inflammationDay 1Macrophage markersHepatic inflammationMouse modelMarker expressionTherapeutic approachesDay 2Day 3Day 7Fibrosis
2023
Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/− mice
Muñoz V, Botezelli J, Gaspar R, da Rocha A, Vieira R, Crisol B, Braga R, Severino M, Nakandakari S, Antunes G, Brunetto S, Ramos C, Velloso L, Simabuco F, de Moura L, da Silva A, Ropelle E, Cintra D, Pauli J. Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/− mice. Cellular And Molecular Life Sciences 2023, 80: 122. PMID: 37052684, PMCID: PMC11072257, DOI: 10.1007/s00018-023-04771-2.Peer-Reviewed Original ResearchConceptsWhole-body glucose homeostasisSkeletal muscle glucose uptakeMuscle glucose uptakeMitochondrial adaptationsMitochondrial activityPost-translational mechanismsSkeletal muscleGlucose uptakeC2C12 cell lineInsulin resistanceStrength exercisesGlucose homeostasisMouse modelPhysical exerciseProtein response markersShort-term physical activityMolecular regulationTranscriptomic modulationRNA sequencingImpact of hyperglycemiaC2C12 cellsStrength exercise trainingType 2 diabetesStrength training protocolsMitochondrial functionInhibition 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
Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise
Brícola R, Cordeiro A, Crisol B, Braga R, de Melo D, Rocha M, Gaspar R, Nakandakari S, Silva V, Anaruma C, Katashima C, Canciglieri R, Munõz V, Pavan I, Pinto A, Simabuco F, da Silva A, Moura L, Pauli J, Cintra D, Ropelle E. Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise. Cell Biochemistry And Function 2022, 41: 128-137. PMID: 36515301, DOI: 10.1002/cbf.3770.Peer-Reviewed Original ResearchConceptsAged miceAdipose tissueControl of lipolysisHigh-intensity interval trainingSubcutaneous white adipose tissueExperimental mouse modelAdipose tissue metabolismWhite adipose tissueMessenger RNA levelsInterval trainingMouse modelTissue metabolismLipolytic pathwayMiceRNA levelsProtein levelsScWATTranscriptomic analyzesReversal effectTissueExerciseSignificant hallmarkLipolysisABHD5Lipolytic activity