Rafael Calais Gaspar, PhD, MSc
Postdoctoral AssociateAbout
Research
Publications
2026
2503-P: The Noradrenergic System Regulates Hepatic Gluconeogenesis, Mitochondrial Oxidation, and Autophagy by CaMKII during Cold Exposure
MORGAN H, GASPAR R, SCHAVINSKI A, ASSIS A, ZHENG J, PARIKH S, DUFOUR S, KAHN M, NASIRI A, PERELIS M, KETTELHUT I, NAVEGANTES L, SHULMAN G. 2503-P: The Noradrenergic System Regulates Hepatic Gluconeogenesis, Mitochondrial Oxidation, and Autophagy by CaMKII during Cold Exposure. Diabetes 2026, 75 DOI: 10.2337/db26-2503-p.Peer-Reviewed Original ResearchHepatic mitochondrial metabolismMitochondrial oxidationHepatic mitochondrial oxidationConversion to glucoseMitochondrial metabolismAntisense oligonucleotidesSao Paulo Research FoundationCold exposureMolecular mechanismsActivation of CaMKIIHepatic gluconeogenesisRate of glycerolGluconeogenesisAutophagyConcentrations of glucoseNoradrenergic systemFatty acidsGlucose productionGlycerolStable isotopesAtg7MetabolismGlucoseTurnoverCaMKIICIDEB and CGI-58 differentially regulate liver lipid-droplet cholesterol to modulate metabolic dysfunction-associated steatohepatitis severity
Sakuma I, Gaspar R, Morgan H, Zheng J, Nasiri A, Dufour S, Kahn M, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Samuel V, Tanaka T, Shulman G. CIDEB and CGI-58 differentially regulate liver lipid-droplet cholesterol to modulate metabolic dysfunction-associated steatohepatitis severity. Cell Reports 2026, 45: 117369. PMID: 42234563, DOI: 10.1016/j.celrep.2026.117369.Peer-Reviewed Original ResearchConceptsCGI-58Protective effectCholesterol levelsL-amino acid-defined high-fat dietLiver-related mortalityLivers of C57BL/6J miceCGI-58 knockdownLipid dropletsCholesterol synthesis inhibitorLipid droplet proteinsCrown-like structuresHigh-fat dietBempedoic acidC57BL/6J miceLiver lipid dropletsPlasma transaminasesCidebCholine-deficientAntisense oligonucleotidesLiverCholesterolAltered cholesterolCholesterol supplementationTriglyceridesKnockdownInsulin receptorT1160 phosphorylation mediates renal cortical insulin resistance but not excess gluconeogenesis from glycerol
Hubbard B, Ma Y, Gaspar R, LaMoia T, Zhang D, Kahn M, Dufour S, Nasiri A, Shulman G. Insulin receptorT1160 phosphorylation mediates renal cortical insulin resistance but not excess gluconeogenesis from glycerol. Nature Communications 2026 PMID: 42168167, DOI: 10.1038/s41467-026-73016-0.Peer-Reviewed Original ResearchHigh-fat dietRenal glucose productionSn-1,2-DAGElevated 6.5-foldImpaired suppression of endogenous glucose productionGlucose productionDysregulated glucose homeostasisMitochondrial metabolismInsulin signalingMitochondrial sourcesInsulin resistanceHigh-fat diet micePyruvate oxidationHFD-fedGlucose homeostasisKnockin miceGluconeogenesisPhosphorylationEndogenous glucose productionRenal gluconeogenesisGlycerolMiceImpaired suppressionMale micePyruvateChanges in weight and metabolic health during and after cessation of a time-restricted feeding plus aerobic training in Swiss mice fed a high-fat diet
Fudoli Lins Vieira R, Castelo Branco Ramos Nakandakari S, Calheiros Antunes G, Azevedo Macedo A, Damasceno de Lima R, da Silva Rios T, Tobar N, Rosetto Muñoz V, Calais Gaspar R, da Silva A, Esper Cintra D, Rochete Ropelle E, Chaix A, Pauli J. Changes in weight and metabolic health during and after cessation of a time-restricted feeding plus aerobic training in Swiss mice fed a high-fat diet. AJP Endocrinology And Metabolism 2026, 330: e431-e441. PMID: 41670954, DOI: 10.1152/ajpendo.00432.2025.Peer-Reviewed Original ResearchConceptsTime-restricted feedingHigh-fat dietMetabolic healthSwiss miceLifestyle interventionFirst-line therapyIntervention cessationHigh-fat diet ad libitumDevelopment of obesityAdipose tissue hypertrophyDiet-induced obesityImpaired glycemic controlUnhealthy eating habitsSwiss male miceWeight gainLower body weightLong-term adherenceSignificant health problemAerobic trainingWeight regainMale miceTissue hypertrophyMetabolic parametersMetabolic improvementGlycemic control
2025
Precancer exercise capacity and metabolism during tumor development coordinate the skeletal muscle–tumor metabolic competition
Leitner B, Fosam A, Lee W, Zilinger K, Nakandakari S, Zhang X, Gaspar R, Zhu W, Perry C, Rabinowitz J, Perry R. Precancer exercise capacity and metabolism during tumor development coordinate the skeletal muscle–tumor metabolic competition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2508707122. PMID: 41325517, PMCID: PMC12704748, DOI: 10.1073/pnas.2508707122.Peer-Reviewed Original ResearchConceptsExercise trainingExercise capacityAerobic exercise trainingRegular exercise trainingHigher exercise capacityMuscle glucose metabolismVoluntary wheel runningTumor progressionGlucose metabolismVoluntary exerciseCardiac muscleExerciseTumor glucose metabolismTumor-host interactionsMetabolic competitionStage of diseaseMuscleCancer prognosisSystemic glucose metabolismTumor energeticsTumor microenvironmentMelanoma tumorsTumor growthTumor developmentTrainingCideb knockdown in mice increases mitochondrial fat oxidation and reverses hepatic steatosis and insulin resistance by the plasma membrane sn-1,2-DAGs–PKCε–insulin receptor kinaseT1150 pathway
Zheng J, Gaspar R, Sakuma I, Hubbard B, Zhang D, Nasiri A, Kahn M, Perelis M, Samuel V, Petersen K, Shulman G. Cideb knockdown in mice increases mitochondrial fat oxidation and reverses hepatic steatosis and insulin resistance by the plasma membrane sn-1,2-DAGs–PKCε–insulin receptor kinaseT1150 pathway. Diabetologia 2025, 68: 2906-2920. PMID: 40908405, DOI: 10.1007/s00125-025-06539-8.Peer-Reviewed Original ResearchMitochondrial fat oxidationWhole-body energy expenditureTricarboxylic acidIn vivo rateHFD-induced hepatic steatosisHigh-fat dietHFD-induced insulin resistanceSteatotic liver diseaseAntisense oligonucleotidesHepatic lipogenesisHepatic mitochondrial oxidationHepatic insulin resistanceCidebHepatic steatosisComprehensive Lab Animal Monitoring SystemHigh-fat diet mouse modelInsulin resistanceMitochondrial oxidationMethodsC57BL/6J male miceRadio-labelled isotopesHyperinsulinaemic–euglycaemic clamp studiesKnockdownASO treatmentLipogenesisConclusions/interpretationThese findingsLiver 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, PMCID: PMC12067271, 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 formNotch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice
Gaspar R, Macêdo A, Nakandakari S, Muñoz V, Abud G, Vieira R, de Sousa Neto I, Pavan I, da Silva L, Simabuco F, da Silva A, Salgado W, Marchini J, Nonino C, Cintra D, Ropelle E, Pajvani U, de Freitas E, Pauli J. Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice. Liver International 2025, 45: e70068. PMID: 40078075, DOI: 10.1111/liv.70068.Peer-Reviewed Original ResearchConceptsNotch1 signalingAerobic exerciseRegulation of hepatic glucoseObese miceImpact of aerobic exerciseEffects of Notch1 signalingAerobic exercise trainingMTORC1 pathway activationNotch1 pathwayObese individualsTissue of obese miceCross-sectional studyNotch1 mRNA levelsMitochondrial respirationExercise trainingLivers of obese individualsTreadmill runningGluconeogenic enzymesHepG2 cell lineLipid accumulationTraining groupHepatic glucoseHepatic metabolismNotch1 proteinPathway activationTime-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice
Macêdo A, de Sousa Neto I, Antonio G, Gaspar R, de Lima R, Dias L, Vieira R, Muñoz V, Brunelli D, da Silva A, Cintra D, Ropelle E, Pauli J. Time-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice. Nutrition 2025, 133: 112691. PMID: 39983606, DOI: 10.1016/j.nut.2025.112691.Peer-Reviewed Original ResearchConceptsRNA-seq datasetsNotch1 intracellular domainMitochondrial respirationTime-restricted feedingAged miceInflammatory markersAd libitum dietIntracellular domainHepatic mitochondrial respirationATP productionLiver mitochondrial respirationCellular longevityLiver of aged miceLibitum dietDisease Activity ScoreCompared to adult animalsNotch1 signalingProtein contentTime-restricted feeding protocolsUpregulation of Notch1Investigated metabolic parametersProtein levelsNotch1Adult miceCollagen fibersDeterminants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals
Pesta D, Anadol-Schmitz E, Sarabhai T, Kamp Y, Gancheva S, Trinks N, Zaharia O, Mastrototaro L, Lyu K, Habets I, Kamp-Bruls Y, Dewidar B, Weiss J, Schrauwen-Hinderling V, Zhang D, Gaspar R, Strassburger K, Kupriyanova Y, Al-Hasani H, Szendroedi J, Schrauwen P, Phielix E, Shulman G, Roden M. Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals. Science Advances 2025, 11: eadr8849. PMID: 39742483, PMCID: PMC11691647, DOI: 10.1126/sciadv.adr8849.Peer-Reviewed Original ResearchConceptsOverweight-to-obeseNormal weightEndurance-trained humansMuscle mitochondrial contentAthlete's paradoxTrained athletesExercise-trainedOverweight individualsAthletesObesity subtypesObservational studyIntramyocellular triglyceride accumulationInsulin sensitivityHigher insulin sensitivityMitochondrial contentIncreased insulin sensitivityMuscleFemale individualsIndividualsInsulin resistanceObesityMitochondrial partitioningIncreased calpainNPKC activityProtein kinase C
News
News
- January 12, 2026
How Exercise Slows Tumor Growth
- July 29, 2025
Study Reveals Cholesterol’s Role in Fibrotic Progression of Metabolic Liver Disease
- February 18, 2025
What Makes a Successful Heart Failure Drug Work?
- April 04, 2023
Researchers Demonstrate New Protective Process Against Liver Fibrosis in NASH
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