2025
ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis
Slusher A, Santoro N, Vash-Margita A, Galderisi A, Hu P, Tokoglu F, Li Z, Tarabra E, Strober J, Vatner D, Shulman G, Caprio S. ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis. Journal Of Clinical Investigation 2025, 135: e184740. PMID: 40091831, PMCID: PMC11910223, DOI: 10.1172/jci184740.Peer-Reviewed Original ResearchConceptsHyperinsulinemic-euglycemic clampSubcutaneous adipose tissueInsulin resistanceAdipose triglyceride lipaseInsulin infusionOral glucose tolerance testAbdominal fat distributionGlucose tolerance testMeasuring abdominal fat distributionLower liver fatActivating adipose triglyceride lipaseMetabolic disease riskLiver fat contentEctopic lipid storageFUNDINGThis workAdipose tissue lipolysisInhibition of adipose tissue lipolysisSubcutaneous adipose tissue samplesFat distributionTolerance testInsulin exposureLiver fatInfusionGlycerol turnoverAdipose tissue
2021
Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis
Gómez-Valadés AG, Pozo M, Varela L, Boudjadja MB, Ramírez S, Chivite I, Eyre E, Haddad-Tóvolli R, Obri A, Milà-Guasch M, Altirriba J, Schneeberger M, Imbernón M, Garcia-Rendueles AR, Gama-Perez P, Rojo-Ruiz J, Rácz B, Alonso MT, Gomis R, Zorzano A, D’Agostino G, Alvarez CV, Nogueiras R, Garcia-Roves PM, Horvath TL, Claret M. Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis. Cell Metabolism 2021, 33: 1820-1835.e9. PMID: 34343501, PMCID: PMC8432968, DOI: 10.1016/j.cmet.2021.07.008.Peer-Reviewed Original ResearchConceptsProtein OPA1Mitochondrial CaMitochondrial cristae architectureAdipose tissue lipolysisKey metabolic sensorPOMC neuronsCellular metabolic adaptationTissue lipolysisCristae architectureMetabolic sensorNutrient availabilityWhite adipose tissue lipolysisAlpha-melanocyte stimulating hormoneGenetic inactivationNovel axisMitochondrial functionOPA1Metabolic adaptationMitochondrial cristaeDramatic alterationsMutant miceProopiomelanocortin neuronsLipolysis controlWAT lipolysisPharmacological blockade
2020
Leptin mediates postprandial increases in body temperature through hypothalamus–adrenal medulla–adipose tissue crosstalk
Perry RJ, Lyu K, Rabin-Court A, Dong J, Li X, Yang Y, Qing H, Wang A, Yang X, Shulman GI. Leptin mediates postprandial increases in body temperature through hypothalamus–adrenal medulla–adipose tissue crosstalk. Journal Of Clinical Investigation 2020, 130: 2001-2016. PMID: 32149734, PMCID: PMC7108915, DOI: 10.1172/jci134699.Peer-Reviewed Original ResearchConceptsBrown adipose tissueLeptin concentrationsBody temperatureAdrenomedullary catecholamine secretionPlasma leptin concentrationsAdipose tissue lipolysisFasting-induced reductionFeeding-induced increaseMeal ingestionPlasma catecholaminesPostprandial increaseCatecholamine secretionObese ratsTissue lipolysisLean ratsAdrenergic activationAdipose tissueTissue crosstalkWeight gainIntragastric infusionRatsLeptinBolusLipolysisFatty acids
2019
Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance
Camporez JP, Lyu K, Goldberg EL, Zhang D, Cline GW, Jurczak MJ, Dixit VD, Petersen KF, Shulman GI. Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance. The Journal Of Physiology 2019, 597: 3885-3903. PMID: 31206703, PMCID: PMC6876753, DOI: 10.1113/jp277270.Peer-Reviewed Original ResearchConceptsObesity-induced insulin resistanceHigh-fat dietEctopic lipid contentWhite adipose tissue lipolysisInsulin resistanceAdipose tissue lipolysisMale miceInsulin sensitivityFemale miceInsulin-stimulated suppressionWAT inflammationTissue lipolysisRodent studiesTumor necrosis factor αWhole-body insulin sensitivityLipid-induced insulin resistanceMetabolic homeostasisAge-matched menInterleukin-6 concentrationsSkeletal muscleAnti-inflammatory effectsType 2 diabetesInsulin-mediated suppressionSexual dimorphic responseNecrosis factor α
2018
Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats
PERRY R, SONG J, WANG Y, SHULMAN G. Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats. Diabetes 2018, 67 DOI: 10.2337/db18-254-or.Peer-Reviewed Original ResearchSodium-glucose transport protein 2 inhibitorsHepatic glucose productionEffect of dapagliflozinEuglycemic ketoacidosisHepatic ketogenesisVolume depletionGlucose productionPlasma catecholaminesWhite adipose tissue lipolysisPlasma glucagon concentrationsExtracellular volume depletionPlasma insulin levelsAdipose tissue lipolysisPlasma insulin concentrationHepatic acetyl-CoA contentNormal Sprague-DawleyICV injectionWAT lipolysisInsulin levelsFurosemide treatmentGlucagon concentrationsAcetyl-CoA contentSaline infusionTissue lipolysisInsulin concentrations
2017
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9172-e9180. PMID: 29073114, PMCID: PMC5664516, DOI: 10.1073/pnas.1707797114.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseDe novo lipogenesisAdipose tissue lipolysisHepatic insulin resistanceThyroid hormonesHypothyroid miceImpaired suppressionInsulin resistanceTissue lipolysisInsulin secretionHigh thyroid-stimulating hormone levelsRegulation of THThyroid-stimulating hormone levelsLipid utilizationFatty liver diseaseSerum glucose levelsEndogenous glucose productionLow thyroid hormoneFatty acidsHepatic lipid utilizationLiver diseaseSevere hypothyroidismHormone levelsProfound suppressionGlucose levels
2013
Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways
Vatner DF, Weismann D, Beddow SA, Kumashiro N, Erion DM, Liao XH, Grover GJ, Webb P, Phillips KJ, Weiss RE, Bogan JS, Baxter J, Shulman GI, Samuel VT. Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways. AJP Endocrinology And Metabolism 2013, 305: e89-e100. PMID: 23651850, PMCID: PMC3725564, DOI: 10.1152/ajpendo.00573.2012.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAnilidesAnimalsDietary FatsFatty LiverGene ExpressionGluconeogenesisGlucose Transporter Type 4HyperglycemiaHyperinsulinismInsulin ResistanceMaleMuscle, SkeletalNon-alcoholic Fatty Liver DiseasePhenolsRatsRats, Sprague-DawleySignal TransductionThyroid Hormone Receptors betaTriglyceridesConceptsEndogenous glucose productionHepatic insulin sensitivityInsulin sensitivityHepatic steatosisFat-fed ratsInsulin-stimulated peripheral glucose disposalTRβ agonistsInsulin-stimulated skeletal muscle glucose uptakePotent lipid-lowering drugsNonalcoholic fatty liver diseaseWhite adipose tissue lipolysisMale Sprague-Dawley ratsSkeletal muscle glucose uptakeGC-1 treatmentPeripheral glucose disposalFatty liver diseaseImpairs insulin sensitivityLipid-lowering drugsHepatic triglyceride contentAdipose tissue lipolysisMuscle glucose uptakeSprague-Dawley ratsHepatic insulin resistanceSkeletal muscle insulinPotential adverse effects
2005
Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training
DiPietro L, Dziura J, Yeckel CW, Neufer PD. Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training. Journal Of Applied Physiology 2005, 100: 142-149. PMID: 16141382, DOI: 10.1152/japplphysiol.00474.2005.Peer-Reviewed Original ResearchConceptsHigh-intensity exercise trainingIntensity exercise trainingExercise trainingAerobic trainingInsulin sensitivityExercise volumeOlder womenGlucose utilizationModerate-intensity aerobic trainingTwo-step euglycemic-hyperinsulinemic clampInsulin-stimulated glucose utilizationHigh-intensity aerobic trainingDual-energy X-ray absorptiometryHigher insulin doseLower insulin doseHealthy older womenEuglycemic hyperinsulinemic clampLow-intensity exerciseTotal body fatAdipose tissue lipolysisImproved glucose utilizationX-ray absorptiometrySuppression of lipolysisFinal exercise boutInsulin-stimulated suppression
2003
Defective Activation of Skeletal Muscle and Adipose Tissue Lipolysis in Type 1 Diabetes Mellitus during Hypoglycemia
Enoksson S, Caprio SK, Rife F, Shulman GI, Tamborlane WV, Sherwin RS. Defective Activation of Skeletal Muscle and Adipose Tissue Lipolysis in Type 1 Diabetes Mellitus during Hypoglycemia. The Journal Of Clinical Endocrinology & Metabolism 2003, 88: 1503-1511. PMID: 12679430, DOI: 10.1210/jc.2002-021013.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAdrenergic beta-AgonistsAdultBlood GlucoseDiabetes Mellitus, Type 1EpinephrineFatty Acids, NonesterifiedFemaleGlucoseGlucose Clamp TechniqueGlycerolHomeostasisHumansHypoglycemiaInsulinLactic AcidLipolysisMaleMuscle, SkeletalNorepinephrineReceptors, Adrenergic, beta-2TerbutalineConceptsT1DM patientsControl subjectsGlucose disposalAdipose tissueType 1 diabetes mellitus patientsWhole-body glucose disposalWhole-body glucose useSkeletal muscleDiabetes mellitus patientsGlucagon secretory responsesRisk of hypoglycemiaPlasma epinephrine concentrationSeverity of hypoglycemiaAdipose tissue lipolysisMajor target tissuesHyperinsulinemic euglycemiaAgonist terbutalineAdrenomedullary responseMellitus patientsNondiabetic subjectsDeficient releasePlasma epinephrinePlasma glucoseInsulin infusionCatecholamine secretion
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