2024
1637-P: TLC-6740, a Liver-Targeted Mitochondrial Protonophore, Increases Energy Expenditure and Lipid Utilization in Obese Mice
SRODA N, VIJAYAKUMAR A, MURAKAMI E, WENG S, SHULMAN G, MYERS R, SUBRAMANIAN M. 1637-P: TLC-6740, a Liver-Targeted Mitochondrial Protonophore, Increases Energy Expenditure and Lipid Utilization in Obese Mice. Diabetes 2024, 73 DOI: 10.2337/db24-1637-p.Peer-Reviewed Original ResearchEnergy intakeWeight lossEnergy expenditureRespiratory exchange ratioMitochondrial protonophoreObese miceDose-dependent weight lossReduced oral intakeData support evaluationDays of dosingC57 BL/6 miceDiet-induced obese miceNegative energy balanceMale C57 BL/6 miceIncreased energy expenditureWhole-body lipid utilizationCompared to pre-treatmentHigh-fat dietOral intakePO BIDBL/6 miceIndirect calorimetryMetabolic benefitsLipid utilizationVEH
2021
IL-27 signalling promotes adipocyte thermogenesis and energy expenditure
Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, Cheng H, Wen Q, Xu H, Zhu L, Zhang H, Perry RJ, Spadaro O, Yang Y, He S, Chen Y, Wang B, Li G, Liu Z, Yang C, Wu X, Zhou L, Zhou Q, Ju Z, Lu H, Xin Y, Yang X, Wang C, Liu Y, Shulman GI, Dixit VD, Lu L, Yang H, Flavell RA, Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature 2021, 600: 314-318. PMID: 34819664, DOI: 10.1038/s41586-021-04127-5.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsBariatric SurgeryDisease Models, AnimalEnergy MetabolismFemaleHumansInsulin ResistanceInterleukin-27MaleMiceObesityP38 Mitogen-Activated Protein KinasesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaReceptors, InterleukinSignal TransductionThermogenesisUncoupling Protein 1ConceptsIL-27Beige adipose tissueAdipose tissueSerum IL-27Diet-induced obesityBariatric surgeryMetabolic morbidityImmunological factorsInsulin resistanceObesity showTherapeutic administrationMetabolic disordersMouse modelObesityPromising targetEnergy expenditureSignaling promotesThermogenesisBody temperatureMetabolic programsImportant roleTissueCritical roleImmunotherapyMorbidityInsulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake
Habtemichael EN, Li DT, Camporez JP, Westergaard XO, Sales CI, Liu X, López-Giráldez F, DeVries SG, Li H, Ruiz DM, Wang KY, Sayal BS, González Zapata S, Dann P, Brown SN, Hirabara S, Vatner DF, Goedeke L, Philbrick W, Shulman GI, Bogan JS. Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake. Nature Metabolism 2021, 3: 378-393. PMID: 33686286, PMCID: PMC7990718, DOI: 10.1038/s42255-021-00359-x.Peer-Reviewed Original ResearchConceptsTUG cleavageGlucose uptakeProtein degradation pathwaysGLUT4 glucose transportersCoactivator PGC-1αC-terminal cleavage productInsulin-stimulated glucose uptakeAte1 arginyltransferaseGene expressionPhysiological relevanceWhole-body energy expenditureGlucose transporterPeroxisome proliferator-activated receptorCell surfacePGC-1αProtein 1Proliferator-activated receptorDegradation pathwayEffect of insulinCleavage pathwayAdipose cellsCleavage productsPathwayCleavageEnergy expenditureAn update on brown adipose tissue biology: a discussion of recent findings
Gaspar RC, Pauli JR, Shulman GI, Muñoz VR. An update on brown adipose tissue biology: a discussion of recent findings. AJP Endocrinology And Metabolism 2021, 320: e488-e495. PMID: 33459179, PMCID: PMC7988785, DOI: 10.1152/ajpendo.00310.2020.Peer-Reviewed Original ResearchConceptsBrown adipose tissueBAT thermogenesisBrown adipose tissue biologyEnergy expenditureBrown-like cellsWhole-body glucoseAdipose tissue biologyBAT metabolismAdrenergic drugsAdipose tissuePotential treatmentThermogenic activityWhite adipocytesBody glucoseFat metabolismEndocrine mechanismsBeneficial roleSecretory moleculesActivity capacityTissue biologyThermogenesisRecent findingsRecent studiesAdditional focusMetabolism
2020
Regulation of adipose tissue inflammation by interleukin 6
Han MS, White A, Perry RJ, Camporez JP, Hidalgo J, Shulman GI, Davis RJ. Regulation of adipose tissue inflammation by interleukin 6. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 2751-2760. PMID: 31980524, PMCID: PMC7022151, DOI: 10.1073/pnas.1920004117.Peer-Reviewed Original ResearchConceptsInterleukin-6Adipose tissue inflammationLow-grade inflammationIndividual cell typesMacrophage infiltrationInflammatory cytokinesTissue inflammationGlucose disposalImmune cellsIL6 productionMouse modelChronic stateAdipose tissueMyeloid cellsTissue infiltrationReceptor αConditional expressionCell typesOxidative metabolismOpposite actionsPhysiological regulationEnergy expenditureCanonical modeInflammationSpecific cells
2001
In Vivo Effects of Uncoupling Protein-3 Gene Disruption on Mitochondrial Energy Metabolism*
Cline G, Vidal-Puig A, Dufour S, Cadman K, Lowell B, Shulman G. In Vivo Effects of Uncoupling Protein-3 Gene Disruption on Mitochondrial Energy Metabolism*. Journal Of Biological Chemistry 2001, 276: 20240-20244. PMID: 11274222, DOI: 10.1074/jbc.m102540200.Peer-Reviewed Original ResearchConceptsATP synthesisEnergy metabolismSkeletal muscleMitochondrial oxidative phosphorylationMitochondrial energy metabolismGene disruptionRatio of ATPOxidative phosphorylationATP productionTricarboxylic acid cycle fluxWhole-body levelUCP3KO miceWhole-body energy expenditureCellular levelProtein 3Cycle fluxLabeling experimentsFirst evidenceBody energy expenditureMetabolismVivoMeasurement of ratesPhosphorylationEnergy expenditureUCP3