2024
Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase
Merali C, Quinn C, Huffman K, Pieper C, Bogan J, Barrero C, Merali S. Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase. Obesity 2024, 32: 2286-2298. PMID: 39420421, DOI: 10.1002/oby.24150.Peer-Reviewed Original ResearchMolecular mechanismsIncreased GLUT4 translocationComplex molecular mechanismsGlucose uptake regulationUBX domainIncreased glucose uptakeGLUT4 translocationGLUT4 functionCaloric restrictionPTGIS expressionProteomic profilingCell surfaceCleavage pathwayInsulin sensitivityHuman adipocytesAdipose tissueGlucose uptakeGLUT4Enhanced insulin sensitivityInsulin receptor densityInsulin actionRisk of metabolic disordersCell membraneProstacyclin synthaseMonths of CRBenefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake
Smith D, Mitchell S, Johnson M, Gibbs V, Dickinson S, Henschel B, Li R, Kaiser K, Chusyd D, Brown A, Allison D, Speakman J, Nagy T. Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake. GeroScience 2024, 46: 4809-4826. PMID: 38850387, PMCID: PMC11336014, DOI: 10.1007/s11357-024-01166-4.Peer-Reviewed Original ResearchProtein intakeCaloric restrictionPair-fedTNF-a levelsMale C57BL/6J miceBenefits of CRFat massC57BL/6J miceLean massTNF-aIGF-1Energy imbalanceMiceCalorie restrictionBenefits of calorie restrictionPhysical activityIntakeLongevity benefitsBody temperatureProtein intake per sePhysiological benefitsProteinLeptinExtended longevityHypothalamusCaloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice
Rinne C, Soultoukis G, Oveisi M, Leer M, Schmidt-Bleek O, Burkhardt L, Bucher C, Moussa E, Makhlouf M, Duda G, Saraiva L, Schmidt-Bleek K, Schulz T. Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice. Frontiers In Endocrinology 2024, 15: 1394263. PMID: 38904042, PMCID: PMC11188307, DOI: 10.3389/fendo.2024.1394263.Peer-Reviewed Original ResearchConceptsBone marrow adipose tissueTrabecular bone lossAged miceCaloric restrictionBone lossEndocrine profileMale C57BL6J miceCardio-metabolic diseasesTime of CRAge-matched littermatesBiochemical lipid profilesAssess bone microstructureFree food accessC57BL6J miceBone healthYoung miceContext of agingMale miceDietary interventionNutritional interventionAnatomical localizationLipid profileAdipogenic gene expressionBone dysfunctionTrabecular bone structure
2023
IMMUNOMETABOLIC CHECKPOINTS OF INFLAMMAGING
Dixit V. IMMUNOMETABOLIC CHECKPOINTS OF INFLAMMAGING. Innovation In Aging 2023, 7: 140-140. PMCID: PMC10735998, DOI: 10.1093/geroni/igad104.0458.Peer-Reviewed Original ResearchCaloric restrictionAnti-inflammatory effectsAnti-inflammatory responseAge-related functional declineNegative energy balanceTissue-resident macrophagesAge-associated degenerative diseasesThymic involutionMaintenance of homeostasisMetabolic dysfunctionFunctional declineAdipose tissueInflammationResident macrophagesStudy participantsDegenerative diseasesMacrophagesKey hallmarksRNA sequence analysisMitochondrial metabolismHuman physiologyUnique regulatorCellular quiescenceMetabolismTranscriptional programsMolecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation.
Bush C, Perry R. Molecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation. Cancer Research 2023, 83: 3493-3494. PMID: 37908187, DOI: 10.1158/0008-5472.can-23-2257.Commentaries, Editorials and LettersConceptsFasting-mimicking dietColorectal cancer progressionIgA class switchingColorectal cancerCancer progressionB cellsClass switchingFatty acid oxidationAnticancer immunityAntitumor immunityImmune therapyMolecular mechanismsTumor regressionMouse modelCaloric restrictionAnticancer effectsMetabolic reprogrammingProgressionDietCancerAcid oxidationCancer researchImmunityMetabolic regulationCellsPolycystic Kidney Disease Diet
Chebib F, Nowak K, Chonchol M, Bing K, Ghanem A, Rahbari-Oskoui F, Dahl N, Mrug M. Polycystic Kidney Disease Diet. Clinical Journal Of The American Society Of Nephrology 2023, 19: 664-682. PMID: 37729939, PMCID: PMC11108253, DOI: 10.2215/cjn.0000000000000326.Peer-Reviewed Original ResearchAutosomal dominant polycystic kidney diseaseDietary interventionCaloric restrictionIntermittent fastingMetabolic healthClinical trialsProgressive kidney function lossUncertain clinical benefitKidney function lossIdeal body weightExtensive clinical researchHigh fluid intakeLimited clinical evidenceDominant polycystic kidney diseasePolycystic kidney diseasePersonalized dietary guidelinesConcentrated sweetsAdverse eventsKetogenic dietClinical benefitClinical evidenceKidney diseaseADPKD progressionWeight managementFavorable outcome207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates
MASTAITIS J, GOMEZ D, LE ROUZIC V, STEC M, KHAN N, NA E, MCWILLIAMS T, MIN S, SLEEMAN M. 207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates. Diabetes 2023, 72 DOI: 10.2337/db23-207-or.Peer-Reviewed Original ResearchIncreased lean massFat massLean massWeight lossGlucagon-like peptide-1 receptor agonistsClinically meaningful weight lossPeptide-1 receptor agonistsBlockade of myostatinCaloric restrictionGLP-1RA treatmentWeeks of treatmentHuman monoclonal antibodyInduce clinically meaningful weight lossMediators of skeletal muscle atrophyStandard-of-careDiet-induced obese miceSkeletal muscle massSkeletal muscle atrophyReduced fat massQuality of weight lossMale cynomolgus monkeysAccelerated weight lossObese patentsReceptor agonistsAnti-obesity agentsEffect 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 absorptiometry
2022
The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.Peer-Reviewed Original ResearchConceptsToll-like receptor 4ISG inductionMatricellular proteinPro-inflammatory phenotypeAnti-inflammatory macrophagesInterferon-stimulated gene expressionAdipocyte-specific deletionInhibition of glycolysisImmunometabolic adaptationsMyD88 pathwayReceptor 4Chronic diseasesFunctional declineCaloric restrictionInterferon responseHealth spanMacrophagesInflammationMitochondrial respirationSPARCInductionGene expressionAdipokinesObesityIFNCaloric restriction in humans reveals immunometabolic regulators of health span
Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Caloric restriction in humans reveals immunometabolic regulators of health span. Science 2022, 375: 671-677. PMID: 35143297, PMCID: PMC10061495, DOI: 10.1126/science.abg7292.Peer-Reviewed Original ResearchMeSH Keywords1-Alkyl-2-acetylglycerophosphocholine EsteraseAdipose TissueAdultAgingAnimalsCaloric RestrictionDown-RegulationEnergy MetabolismFemaleHumansImmune SystemInflammasomesInflammationLongevityLymphopoiesisMacrophagesMaleMiceMiddle AgedMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinThermogenesisThymus GlandTranscriptomeConceptsCaloric restrictionAge-related inflammationHealth spanAnti-inflammatory responseNLRP3 inflammasome activationEctopic lipidsMetabolic healthInflammasome activationHealthy humansAdipose tissueImmunometabolic effectsFactor acetyl hydrolaseImmune defenseInflammationAcetyl hydrolaseMitochondrial bioenergeticsHumansLife spanLipoatrophyPLA2G7ThymopoiesisMiceTick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock
Minteer C, Morselli M, Meer M, Cao J, Higgins‐Chen A, Lang SM, Pellegrini M, Yan Q, Levine ME. Tick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock. Aging Cell 2022, 21: e13553. PMID: 35104377, PMCID: PMC8844113, DOI: 10.1111/acel.13553.Peer-Reviewed Original ResearchConceptsMouse embryonic fibroblastsDNA methylationEpigenetic agingImportant chromatin regulatorsPolycomb group (PcG) factorsAnti-aging interventionsChromatin regulatorsEmbryonic fibroblastsCellular senescenceTissue agingCellular agingEpigenetic clocksMultiple tissuesMouse tissuesCaloric restrictionMechanistic insightsAging changesKidney fibroblastsReduced representationTime pointsPhysiological agingMouse culturesSuch alterationsTick-TockTissue
2021
The Breast Cancer Weight Loss trial (Alliance A011401): A description and evidence for the lifestyle intervention
Delahanty LM, Wadden TA, Goodwin PJ, Alfano CM, Thomson CA, Irwin ML, Neuhouser ML, Crane TE, Frank E, Spears PA, Gillis BP, Hershman DL, Paskett ED, Hopkins J, Bernstein V, Stearns V, White J, Hudis C, Winer EP, Carey L, Partridge AH, Ligibel JA. The Breast Cancer Weight Loss trial (Alliance A011401): A description and evidence for the lifestyle intervention. Obesity 2021, 30: 28-38. PMID: 34932888, PMCID: PMC9186690, DOI: 10.1002/oby.23287.Peer-Reviewed Original ResearchConceptsWeight loss interventionWeight loss trialLifestyle interventionHealth education materialsWeight lossLoss trialPhysical activityInvasive disease-free survivalDisease-free survivalBreast cancer patientsBreast cancer diagnosisCare of thousandsEducation materialsBaseline weightCancer outcomesCancer patientsHealth coachesCancer recurrenceBreast cancerCaloric restrictionStage IITrialsCancer diagnosisInterventionWomen
2016
Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism
Kim KE, Jung Y, Min S, Nam M, Heo RW, Jeon BT, Song DH, Yi CO, Jeong EA, Kim H, Kim J, Jeong SY, Kwak W, Ryu do H, Horvath TL, Roh GS, Hwang GS. Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism. Scientific Reports 2016, 6: 30111. PMID: 27439777, PMCID: PMC4954985, DOI: 10.1038/srep30111.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseDb/db miceDb miceEffects of CRCaloric restrictionLiver diseaseHepatic steatosisHepatic metabolismObese diabetic db/db miceBody weightDiabetic db/db miceFatty liver diseaseObesity-related diseasesInflammation-related proteinsSignificant metabolic alterationsMultiple pathological mechanismsEndoplasmic reticulum stressWestern blot analysisMultiple complicationsInsulin resistanceLipocalin-2Metabolic dysfunctionTherapeutic effectFrequent causeClinical problemProlongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution
Youm YH, Horvath TL, Mangelsdorf DJ, Kliewer SA, Dixit VD. Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 1026-1031. PMID: 26755598, PMCID: PMC4743827, DOI: 10.1073/pnas.1514511113.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationAge-related thymic involutionCaloric restrictionFGF21 functionThymic involutionThymic agingHormone fibroblast growth factor 21Peripheral T-cell diversityThymic T-cell exportFibroblast growth factor 21Diverse T cell repertoireCortical thymic epithelial cellsLow immune competenceT cell frequenciesStem cell transplantationGrowth factor 21Naïve T cellsMiddle-aged miceT cell repertoireT cell diversityThymic stromal cellsT cell exportThymic epithelial cellsBrown adipose tissueEarly thymocyte progenitors
2014
Diet, microbiota and autoimmune diseases
Vieira S, Pagovich O, Kriegel M. Diet, microbiota and autoimmune diseases. Lupus 2014, 23: 518-526. PMID: 24763536, PMCID: PMC4009622, DOI: 10.1177/0961203313501401.Peer-Reviewed Original ResearchConceptsAutoimmune diseasesGut microbial communityGerm-free mouse modelDevelopment of autoimmunityDiet-derived metabolitesType 1 diabetesSeverity of diseaseLife-prolonging effectAdaptive immune systemAntiphospholipid syndromeAutoimmune modelSystemic lupusMultiple sclerosisGastrointestinal tractMurine modelMouse modelRodent modelsImmunomodulatory potentialCommensal bacteriaImmune systemCaloric restrictionGut microbiomeDietary changesLupusGut commensals
2013
Demystifying the “Magical Cure” for Diabetes
Jastreboff A. Demystifying the “Magical Cure” for Diabetes. Science Translational Medicine 2013, 5 DOI: 10.1126/scitranslmed.3006449.Peer-Reviewed Original Research
1976
Clinical Semi-Starvation — Depression of Hypoxic Ventilatory Response
Doekel R, Zwillich C, Scoggin C, Kryger M, Weil J. Clinical Semi-Starvation — Depression of Hypoxic Ventilatory Response. New England Journal Of Medicine 1976, 295: 358-361. PMID: 819829, DOI: 10.1056/nejm197608122950703.Peer-Reviewed Original ResearchConceptsHypoxic ventilatory responseVentilatory responseHypercapnic ventilatory responseMetabolic rateRespiratory failureIntravenous fluidsDecreased metabolic rateCarbohydrate dietNormal subjectsCaloric restrictionDay 10HypercapniaSupplemental electrolytesResponse responseSubjectsResponseHypoxemiaDecreaseHypoxiaAlimentation
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