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 isotopesAtg7MetabolismGlucoseTurnoverCaMKII2486-P: Hepatic Knockdown of ANT2 Promotes Increased Hepatic Fat Oxidation by Upregulation of Uncoupling Protein 3
ZHENG J, GASPAR R, MORGAN H, PARIKH S, PERELIS M, SAMUEL V, PETERSEN K, SHULMAN G. 2486-P: Hepatic Knockdown of ANT2 Promotes Increased Hepatic Fat Oxidation by Upregulation of Uncoupling Protein 3. Diabetes 2026, 75 DOI: 10.2337/db26-2486-p.Peer-Reviewed Original ResearchUncoupling protein 3Hepatic mitochondrial oxidationMitochondrial uncouplingMitochondrial oxidationGluconeogenic fluxChemical mitochondrial uncouplersMitochondrial oxidative metabolismANT2 expressionProtein 3Oxidative metabolismMitochondrial metabolismTranscriptome analysisWhole-body energy expenditureOxidative phosphorylationMitochondrial ATPANT2Cytosolic ADPFat oxidationMetabolic phenotypeHepatic fat oxidationHepatic oxidative metabolismPotential new strategyCarrier 2Energy metabolismATP depletion1790-P: TLC-1180 Enhances Liver, Muscle, WAT, and Myocardial Insulin Sensitivity and Increases Exercise Capacity in DIO Mice
PARIKH S, SHARMA M, GASPAR R, HUANG X, ZHANG D, DUFOUR S, MORGAN H, NASIRI A, ZHENG J, KAHN M, STACK J, MYERS R, SUBRAMANIAN G, VIJAYAKUMAR A, SHULMAN G. 1790-P: TLC-1180 Enhances Liver, Muscle, WAT, and Myocardial Insulin Sensitivity and Increases Exercise Capacity in DIO Mice. Diabetes 2026, 75 DOI: 10.2337/db26-1790-p.Peer-Reviewed Original ResearchHyperinsulinemic-euglycemic clampWhite adipose tissueInsulin resistanceExercise capacityDIO miceGraded exercise testMaximal running speedInsulin sensitivityIncreased exercise capacityPreserved Ejection FractionSuppression of endogenous glucose productionWhole-body insulin sensitivityMyocardial insulin sensitivityInsulin-stimulated 2-DG uptakeVisceral white adipose tissueExercise performanceCardiac fitnessWhole-body insulin resistanceExercise testPathogenesis of T2DExercise durationEjection fractionPreclinical findingsLean controlsCardiac function3064-LB: Mitochondrial Protonophore TLC-1180 Mitigates Cognitive Decline in Diet-Induced Obese Mice
GASPAR R, MORGAN H, PARIKH S, FURTADO J, ISAZA J, ZHENG J, SUCUPIRA F, SHARMA M, MYERS R, SUBRAMANIAN G, VIJAYAKUMAR A, PANE M, SHULMAN G. 3064-LB: Mitochondrial Protonophore TLC-1180 Mitigates Cognitive Decline in Diet-Induced Obese Mice. Diabetes 2026, 75 DOI: 10.2337/db26-3064-lb.Peer-Reviewed Original ResearchNovel object recognition testOpen field testNeuronal activityCognitive declineHigh-fat dietImpaired recognition memoryRecognition memory performanceC-Fos-positive cellsObject recognition testC-Fos immunohistochemistryC-fosC-fos expressionRecognition memoryMale C57BL/6J miceMemory performanceBehavioral deficitsBehavioral performanceRecognition testRegular chowExploratory activitySucrose intakeCognitive performanceCognitive behaviorExploratory behaviorPharmacological correctionCIDEB 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 micePyruvateWestern diet-induced MASH in PWK/PhJ mice identifies disruptions in amino acid and sphingolipid metabolism contributing to cardiac dysfunction
Rodríguez-López S, Pérez-Rodríguez M, Badreddine A, Gaspar R, Novaes Morgan H, Sakuma I, von Alvensleben G, Alonso-Calleja A, Everts S, Suter N, Benegiamo G, Goepfert C, de Brot S, Villalba J, Shulman G, Schoonjans K, Auwerx J. Western diet-induced MASH in PWK/PhJ mice identifies disruptions in amino acid and sphingolipid metabolism contributing to cardiac dysfunction. Nature Communications 2026 PMID: 42156763, DOI: 10.1038/s41467-026-73449-7.Peer-Reviewed Original ResearchWestern dietCardiac dysfunctionCardiovascular diseaseMolecular profilingMetabolic changesAmino acidsCardio-metabolic disordersAssociated with cardiovascular diseaseHepatic synthesisSynthesis of ceramideCardiovascular disease riskSteatotic liver diseaseElevated cholesterol levelsExposure to WDPWK/PhJ strainAssociated with translationHepatic lipid accumulationMouse strainsMitochondrial metabolismHepatic fibrosisLiver diseaseTranscriptional profilesCholesterol levelsLiver disordersPWK/PhJChanges 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 findings
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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