2025
1686-P: Novel Combination of a Mitochondrial Protonophore (MP) and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice
SRODA N, SHARMA M, MURAKAMI E, LOGAN C, WENG S, KIRBY B, MYERS R, SUBRAMANIAN M, SHULMAN G, VIJAYAKUMAR A. 1686-P: Novel Combination of a Mitochondrial Protonophore (MP) and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice. Diabetes 2025, 74 DOI: 10.2337/db25-1686-p.Peer-Reviewed Original ResearchLean massMitochondrial protonophoreDIO miceFood intakeFat mass lossReduced lean massWeight lossBody weightAcetyl-CoA carboxylase 2Obesity-associated disordersMale DIO miceFat massSemaglutideDiet-inducedNovel combinationObese miceMetabolic disordersEnhanced fatty acid oxidationMiceFatty acid oxidationEvaluation of combinationsObesityInhibitorsTreated withIntake1687-P: Sequential Combination of the Mitochondrial Protonophore (MP) TLC-6740 with Semaglutide Normalizes Body Weight and Preserves Lean Mass in DIO Mice
SRODA N, SHARMA M, MURAKAMI E, LOGAN C, WENG S, KIRBY B, MYERS R, SUBRAMANIAN M, SHULMAN G, VIJAYAKUMAR A. 1687-P: Sequential Combination of the Mitochondrial Protonophore (MP) TLC-6740 with Semaglutide Normalizes Body Weight and Preserves Lean Mass in DIO Mice. Diabetes 2025, 74 DOI: 10.2337/db25-1687-p.Peer-Reviewed Original ResearchLean massDIO miceFM lossBody weightMitochondrial protonophoreData support evaluationNormal body weightReduced food intakeRegulate body weightOral glucose toleranceEvaluate weight lossIncreased energy expenditureMale DIO miceSequential combinationDiet-inducedFood intakeGlucose toleranceMetabolic disordersSemaglutideMiceWeight lossEnergy expenditureOGTTOGTT AUCIncretin1694-P: De Novo or Sequential Combination of the Mitochondrial Protonophore TLC-1180 with Semaglutide Improves Weight Loss and Preserves Lean Mass in Dio Mice
SHARMA M, SRODA N, MURAKAMI E, LOGAN C, WENG S, KIRBY B, MYERS R, SUBRAMANIAN M, SHULMAN G, VIJAYAKUMAR A. 1694-P: De Novo or Sequential Combination of the Mitochondrial Protonophore TLC-1180 with Semaglutide Improves Weight Loss and Preserves Lean Mass in Dio Mice. Diabetes 2025, 74 DOI: 10.2337/db25-1694-p.Peer-Reviewed Original Research
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 roleImmunotherapyMorbidity
2020
Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance
He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. Journal Of Experimental Medicine 2020, 218: e20201416. PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAnimalsDiabetes Mellitus, Type 2Diet, High-FatEnergy MetabolismFatty LiverGene DeletionGene TargetingGluconeogenesisHomeostasisHumansHyperglycemiaInflammationInsulin ResistanceLipogenesisLiverMaleMice, Inbred C57BLMice, KnockoutMitochondriaMitophagyNF-kappa BOxidative StressPhenotypeReactive Oxygen SpeciesSequestosome-1 ProteinSignal TransductionThioredoxinsConceptsHepatic insulin resistanceWhite adipose tissueInsulin resistanceAdipose inflammationType 2 diabetes mellitusLipid metabolic disordersNF-κB inhibitorAdipose-specific deletionWhole-body energy homeostasisAltered fatty acid metabolismFatty acid metabolismT2DM progressionT2DM patientsDiabetes mellitusReactive oxygen species pathwayHepatic steatosisMetabolic disordersNF-κBP62/SQSTM1Adipose tissueHuman adipocytesEnergy homeostasisExcessive mitophagyOxygen species pathwayInflammation
2019
The integrative biology of type 2 diabetes
Roden M, Shulman GI. The integrative biology of type 2 diabetes. Nature 2019, 576: 51-60. PMID: 31802013, DOI: 10.1038/s41586-019-1797-8.Peer-Reviewed Original ResearchConceptsType 2 diabetesInsulin resistanceFrequent metabolic disorderWhite adipose tissueRelevant animal modelsCommon underlying abnormalityAdequate substrate supplyInflammatory pathwaysUnderlying abnormalityMetabolic disordersAnimal modelsAdipose tissueEnergy intakeHepatic gluconeogenesisDiabetesObesityAbnormalitiesTissue communicationRecent studiesEnergy imbalanceDysfunctionPathwayInsulinIntakeBrain
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