2024
The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose
Mashayekhi M, Sheng Q, Bailin S, Massier L, Zhong J, Shi M, Wanjalla C, Wang T, Ikizler T, Niswender K, Gabriel C, Palacios J, Turgeon‐Jones R, Reynolds C, Luther J, Brown N, Das S, Dahlman I, Mosley J, Koethe J, Rydén M, Bachmann K, Shah R. The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose. Obesity 2024, 32: 1526-1540. PMID: 38967296, PMCID: PMC11269023, DOI: 10.1002/oby.24064.Peer-Reviewed Original ResearchVisceral adipose tissueExpression quantitative trait lociSubcutaneous adipose tissueGenetic effect sizesQuantitative trait lociInsulin resistanceAdipocyte transcriptsSat geneAdipose transcriptomeTrait lociTranscriptional architectureTranscriptional landscapeMetabolic bufferRNA sequencingInsulin stimulationAdipose tissueNon-immune cell populationsMetabolic phenotypeWeight loss surgeryNon-immune populationSpectrum of obesityCardiometabolic disease riskMacrophage transcriptionMolecular signaturesType 2 diabetes
2023
Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes.
Mashayekhi M, Nian H, Mayfield D, Devin J, Gamboa J, Yu C, Silver H, Niswender K, Luther J, Brown N. Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes. Diabetes 2023, 73: 38-50. PMID: 37874653, PMCID: PMC10784656, DOI: 10.2337/db23-0356.Peer-Reviewed Original ResearchConceptsEndogenous GLP-1Glucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsImproved insulin sensitivityInsulin sensitivityGLP-1GLP-1RGlucagon levelsGlucose levelsMatsuda indexWeight lossHypocaloric dietPostprandial glucoseInhibitor sitagliptinReceptor agonistMetabolic effectsDiet-induced weight lossDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent effectsDPP-4 inhibitor sitagliptinDipeptidyl peptidase-4 inhibitionPeptidase-4 inhibitionMixed meal testGLP-1R antagonistEffect of the glucagon‐like peptide‐1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes
Silver H, Olson D, Mayfield D, Wright P, Nian H, Mashayekhi M, Koethe J, Niswender K, Luther J, Brown N. Effect of the glucagon‐like peptide‐1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes. Diabetes Obesity And Metabolism 2023, 25: 2340-2350. PMID: 37188932, PMCID: PMC10544709, DOI: 10.1111/dom.15113.Peer-Reviewed Original ResearchMeSH KeywordsAdultAppetiteBody Fat DistributionBody WeightCaloric RestrictionCardiovascular DiseasesDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsDipeptidyl-Peptidases and Tripeptidyl-PeptidasesEatingGlucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsLiraglutideObesityPrediabetic StateSitagliptin PhosphateWeight LossConceptsGlucagon-like peptide-1 receptor agonist liraglutidePeptide-1 receptor agonist liraglutideLiraglutide groupSitagliptin groupCR groupCaloric restrictionChi-squared testDietary intakeWeight lossBody weightBody compositionDipeptidyl peptidase-4 inhibitor sitagliptinDipeptidyl peptidase-4 inhibitorsDual-energy X-ray absorptiometryEnergy X-ray absorptiometryInsulin resistance scoreBaseline body weightHomeostatic model assessmentPeptidase-4 inhibitorsCardiometabolic risk reductionBody fat distributionVisual analog scaleWeeks of interventionPersonal risk factorsX-ray absorptiometryBradykinin B2 receptor blockade and intradialytic hypotension
Gamboa J, Mambungu C, Clagett A, Nian H, Yu C, Ikizler T, Brown N. Bradykinin B2 receptor blockade and intradialytic hypotension. BMC Nephrology 2023, 24: 134. PMID: 37170244, PMCID: PMC10176680, DOI: 10.1186/s12882-023-03192-4.Peer-Reviewed Original ResearchConceptsBradykinin B2 receptor blockadeB2 receptor blockadeMaintenance hemodialysisBlood pressureReceptor blockersReceptor blockadeIntradialytic hypotensionBradykinin B2 receptor blockerLack of vasoconstrictionProduction of vasodilatorsSystolic blood pressureGroup of patientsCrossover clinical trialCommon clinical complicationHemodynamic effectsClinical complicationsContinuous infusionClinical trialsStratified analysisIcatibantHemodialysisPatientsHypotensionPlaceboCompensatory mechanismsObesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network
Clark J, Garvey W, Niswender K, Schmidt A, Ahima R, Aleman J, Battarbee A, Beckman J, Bennett W, Brown N, Chandler‐Laney P, Cox N, Goldberg I, Habegger K, Harper L, Hasty A, Hidalgo B, Kim S, Locher J, Luther J, Maruthur N, Miller E, Sevick M, Wells Q. Obesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network. Journal Of The American Heart Association 2023, 12: e027693. PMID: 36752232, PMCID: PMC10111504, DOI: 10.1161/jaha.122.027693.Peer-Reviewed Original ResearchConceptsAmerican Heart AssociationHeart AssociationWeight loss interventionNovel therapeutic approachesVanderbilt University Medical CenterUniversity Medical CenterEffective therapeutic interventionsField of obesityResearch NetworkLoss interventionClinical trialsWorldwide prevalenceMedical CenterTherapeutic approachesObesityTherapeutic targetAnimal modelsJohns Hopkins University SchoolTherapeutic interventionsIndividual centersNew targetsUniversity of AlabamaOverweightUniversity SchoolInterventionCancer Therapy–Related Hypertension: A Scientific Statement From the American Heart Association
Cohen J, Brown N, Brown S, Dent S, van Dorst D, Herrmann S, Lang N, Oudit G, Touyz R, Arteriosclerosis T. Cancer Therapy–Related Hypertension: A Scientific Statement From the American Heart Association. Hypertension 2023, 80: e46-e57. PMID: 36621810, PMCID: PMC10602651, DOI: 10.1161/hyp.0000000000000224.Peer-Reviewed Original ResearchConceptsCardiovascular toxicityVascular endothelial growth factor inhibitorsCancer therapyEvidence-based clinical trialsNational hypertension guidelinesVascular endothelial growth factor receptorCardiovascular risk factorsDiscontinuation of treatmentCommon side effectsGrowth factor inhibitorsEndothelial growth factor receptorPrimary care professionalsAmerican Heart AssociationTyrosine kinase inhibitorsOptimal therapeutic effectNitric oxide generationGrowth factor receptorHypertension specialistsHypertension guidelinesSympathetic outflowAdjunctive therapyCardiovascular mortalityEndothelial dysfunctionHormone therapyBlood pressure
2022
Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial
Mashayekhi M, Beckman JA, Nian H, Garner EM, Mayfield D, Devin JK, Koethe JR, Brown JD, Cahill KN, Yu C, Silver H, Niswender K, Luther JM, Brown NJ. Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial. Diabetes Obesity And Metabolism 2022, 25: 570-580. PMID: 36306151, PMCID: PMC10306232, DOI: 10.1111/dom.14903.Peer-Reviewed Original ResearchConceptsFlow-mediated vasodilationPlasminogen activator inhibitor-1Vascular endothelial functionEndothelial functionInsulin resistanceWeight lossGlucagon-like peptide-1 receptor agonistsBaseline flow-mediated vasodilationDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent mechanismsPeptide-1 receptor agonistsBeneficial effectsEndothelial vasodilator functionGreater endothelial dysfunctionIncretin-based therapiesNormal endothelial functionChemoattractant protein-1Chemokine MCP-1Significant weight lossActivator inhibitor-1Effect of treatmentVasodilator functionUrine albuminEndothelial dysfunctionComparison of Pharmacy Refill Data With Chemical Adherence Testing in Assessing Medication Nonadherence in a Safety Net Hospital Setting
Osula D, Wu B, Schesing K, Das SR, Moss E, Alvarez K, Clark C, Halm EA, Brown NJ, Vongpatanasin W. Comparison of Pharmacy Refill Data With Chemical Adherence Testing in Assessing Medication Nonadherence in a Safety Net Hospital Setting. Journal Of The American Heart Association 2022, 11: e027099. PMID: 36193931, PMCID: PMC9673714, DOI: 10.1161/jaha.122.027099.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsCalcium Channel BlockersCross-Sectional StudiesHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypertensionMedication AdherencePharmacySafety-net ProvidersSodium Chloride Symporter InhibitorsConceptsEnzyme inhibitors/angiotensin receptor blockersAngiotensin receptor blockersCalcium channel blockersReceptor blockersPositive predictive valueUncontrolled hypertensionBeta blockersMedication nonadherenceAntihypertensive drugsDrug classesChannel blockersAngiotensin-converting enzyme inhibitors/angiotensin receptor blockersPredictive valueAdherence testingSafety-net hospital settingSafety-net health systemLow positive predictive valuePharmacy refill dataProportion of daysCross-sectional studyPlasma drug levelsDiagnostic test characteristicsPharmacy fill dataCommon cardiovascular drugsRefill dataProneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma
Eugster PJ, Maurer J, Vocat C, Abid K, Matter M, Wuerzner G, Trepp R, Fischli S, Henzen C, Kolb W, Bilz S, Sigrist S, Beuschlein F, Nölting S, Reul A, Schütze I, Hubers SA, Brown NJ, Grouzmann E. Proneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma. Clinica Chimica Acta 2022, 534: 146-155. PMID: 35905838, DOI: 10.1016/j.cca.2022.07.018.Peer-Reviewed Original ResearchConceptsUpper reference limitPlasma free metanephrinesNeuropeptide YSevere kidney impairmentFree metanephrinesNPY3-36Kidney impairmentSympathetic nervesCatecholamine reuptakeVasoconstrictor peptideNPY2-36NPY1-36Early diagnosisHealthy volunteersPPGL patientsAdrenal medullaTumor localizationPatientsNPYReference limitsDiagnostic sensitivityPPGLsGold standardReference intervalsPheochromocytomaGlucagon-Like Peptide-1 Receptor Regulates Thromboxane-Induced Human Platelet Activation
Cahill KN, Amin T, Boutaud O, Printz R, Newcomb DC, Foer D, Hodson DJ, Broichhagen J, Beckman JA, Yu C, Nian H, Mashayekhi M, Silver HJ, Luther JM, Brown NJ, Peebles RS, Niswender K. Glucagon-Like Peptide-1 Receptor Regulates Thromboxane-Induced Human Platelet Activation. JACC Basic To Translational Science 2022, 7: 713-715. PMID: 35958685, PMCID: PMC9357570, DOI: 10.1016/j.jacbts.2022.04.004.Peer-Reviewed Original ResearchDPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment
Wilson JR, Garner EM, Mashayekhi M, Hubers SA, Bustamante C, Kerman SJ, Nian H, Shibao CA, Brown NJ. DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment. Hypertension 2022, 79: 827-835. PMID: 35045722, PMCID: PMC8917054, DOI: 10.1161/hypertensionaha.121.18348.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAngiotensinsAprepitantBlood PressureCardiovascular AgentsCatecholaminesCross-Over StudiesDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4HumansNorepinephrineRamiprilRenin-Angiotensin SystemSitagliptin PhosphateValsartanConceptsDPP4 inhibitionBlood pressureACE inhibitionDouble-blind crossover studyAcute ACE inhibitionBlood pressure armNK1 receptor blockerACE inhibitor treatmentOral diabetes medicationsCalcium channel blockersType 2 diabetesEffects of DPP4Aldosterone systemCardiovascular complicationsDiabetes medicationsReceptor blockersCardiovascular effectsCrossover therapyHeart failureHypotensive effectCrossover studyChannel blockersDPP4 inhibitorsHeart rateInhibitor treatment
2021
The soluble epoxide hydrolase inhibitor GSK2256294 decreases the proportion of adipose pro-inflammatory T cells
Mashayekhi M, Wanjalla CN, Warren CM, Simmons JD, Ghoshal K, Pilkinton M, Bailin SS, Gabriel CL, Pozzi A, Koethe JR, Brown NJ, Kalams SA, Luther JM. The soluble epoxide hydrolase inhibitor GSK2256294 decreases the proportion of adipose pro-inflammatory T cells. Prostaglandins And Other Lipid Mediators 2021, 158: 106604. PMID: 34922004, PMCID: PMC8742790, DOI: 10.1016/j.prostaglandins.2021.106604.Peer-Reviewed Original ResearchConceptsPro-inflammatory T cellsEpoxyeicosatrienoic acidsSoluble epoxide hydrolaseSystemic inflammationT cellsAdipose tissueSubcutaneous abdominal adipose tissueEnzyme soluble epoxide hydrolaseComplex immune environmentT cell profileAbdominal adipose tissuePrediabetic adultsImmune environmentObese individualsSEH inhibitionObese personsTumor necrosisObese animalsInflammationCrossover designCell profilesGSK2256294Epoxide hydrolaseCentral contributorTissueGSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans
Luther JM, Ray J, Wei D, Koethe JR, Hannah L, DeMatteo A, Manning R, Terker AS, Peng D, Nian H, Yu C, Mashayekhi M, Gamboa J, Brown NJ. GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans. Hypertension 2021, 78: 1092-1102. PMID: 34455816, PMCID: PMC8429121, DOI: 10.1161/hypertensionaha.121.17659.Peer-Reviewed Original ResearchAssociation of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program
Akwo EA, Robinson-Cohen C, Chung CP, Shah SC, Brown NJ, Ikizler TA, Wilson OD, Rowan BX, Shuey MM, Siew ED, Luther JM, Giri A, Hellwege JN, Edwards D, Roumie CL, Tao R, Tsao PS, Gaziano JM, Wilson PWF, O’Donnell C, Edwards TL, Kovesdy CP, Hung AM, Program O. Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program. Hypertension 2021, 78: 376-386. PMID: 34148359, PMCID: PMC8364328, DOI: 10.1161/hypertensionaha.120.16181.Peer-Reviewed Original ResearchActive B-Type Natriuretic Peptide Measured by Mass Spectrometry and Response to Sacubitril/Valsartan
Dillon EM, Wei SD, Gupta DK, Nian H, Rodibaugh BS, Bachmann KN, Naftilan AJ, Stevenson LW, Brown NJ. Active B-Type Natriuretic Peptide Measured by Mass Spectrometry and Response to Sacubitril/Valsartan. Journal Of Cardiac Failure 2021, 27: 1231-1239. PMID: 34133968, PMCID: PMC8578199, DOI: 10.1016/j.cardfail.2021.05.026.Peer-Reviewed Original ResearchConceptsSacubitril/valsartanSacubitril/valsartan treatmentHeart failureBNP1-32NT-proBNPValsartan treatmentActive B-type natriuretic peptideEnd-stage renal diseaseB-type natriuretic peptideNT-proBNP immunoassaysPg/mLRenal diseaseNatriuretic peptideBNP productionHealthy volunteersBNPPg/ValsartanPatientsInhibition of degradationPeptide immunoassayBNP degradationTreatmentImmunoassayMS accountsTreatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids
Luther JM, Wei DS, Ghoshal K, Peng D, Adler GK, Turcu AF, Nian H, Yu C, Solorzano CC, Pozzi A, Brown NJ. Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids. Hypertension 2021, 77: 1323-1331. PMID: 33583202, PMCID: PMC8320355, DOI: 10.1161/hypertensionaha.120.14808.Peer-Reviewed Original ResearchConnecting Generations of Scientists in the Council on Hypertension Through Harriet Dustan
Watts SW, Alexander BT, Baylis C, Brown NJ, Cassis LA, Denton KM, Joe B, Lerman LO, Oparil S, Reckelhoff JF, Sandberg K, Touyz RM. Connecting Generations of Scientists in the Council on Hypertension Through Harriet Dustan. Hypertension 2021, 77: 296-307. PMID: 33390045, PMCID: PMC7856247, DOI: 10.1161/hypertensionaha.120.16623.Peer-Reviewed Original Research
2020
Promoting the success of women and minority physician-scientists in academic medicine: a dean’s perspective
Brown NJ. Promoting the success of women and minority physician-scientists in academic medicine: a dean’s perspective. Journal Of Clinical Investigation 2020, 130: 6201-6203. PMID: 33021966, PMCID: PMC7685745, DOI: 10.1172/jci144526.Peer-Reviewed Original ResearchAssociation of a glucagon‐like peptide‐1 receptor gene variant with glucose response to a mixed meal
Mashayekhi M, Wilson JR, Jafarian‐Kerman S, Nian H, Yu C, Shuey MM, Luther JM, Brown NJ. Association of a glucagon‐like peptide‐1 receptor gene variant with glucose response to a mixed meal. Diabetes Obesity And Metabolism 2020, 23: 281-286. PMID: 33001556, PMCID: PMC8142152, DOI: 10.1111/dom.14216.Peer-Reviewed Original ResearchConceptsGlucagon-like peptide-1Endogenous glucagon-like peptide-1DPP-4 inhibitor sitagliptinDipeptidyl peptidase-4 inhibitorsType 2 diabetes mellitusIntact GLP-1 levelsMixed-meal studyGLP-1 levelsPostprandial glucose excursionsPeptidase-4 inhibitorsDPP-4 inhibitionMetabolic responseGLP-1 receptorReceptor gene variantsSitagliptin treatmentDiabetes mellitusMeal studyPostprandial glucoseInhibitor sitagliptinGlucose excursionsMixed mealPeptide-1Glucose responseGenotype groupsGene variantsExome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker–Induced Angioedema
Maroteau C, Siddiqui M, Veluchamy A, Carr F, White M, Cassidy AJ, Baranova EV, Rasmussen ER, Eriksson N, Bloch KM, Brown NJ, Bygum A, Hallberg P, Karawajczyk M, Magnusson PKE, Yue Q, Syvänen A, von Buchwald C, Alfirevic A, der Zee A, Wadelius M, Palmer CNA, PREDICTION‐ADR. Exome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker–Induced Angioedema. Clinical Pharmacology & Therapeutics 2020, 108: 1195-1202. PMID: 32496628, PMCID: PMC10306231, DOI: 10.1002/cpt.1927.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngioedemaAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsCase-Control StudiesDNA Mutational AnalysisEuropeExomeExome SequencingFactor VFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedMutation RateMutation, MissenseRisk AssessmentRisk FactorsUnited StatesConceptsAngiotensin receptor blockersACEi-AEReceptor blockersLife-threatening adverse reactionsMissense variantsRare variantsCommon variantsRare missense variantsGene risk scoreACE inhibitorsAdverse reactionsDeleterious missense variantsHigh riskRisk scoreAngioedemaEnzyme inhibitorsNeck regionExome sequencingAsian populationsDifferent centersBlood clottingBlockersF5 geneRiskInhibitors