2024
The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity
Laughlin M, McIndoe R, Adams S, Araiza R, Ayala J, Kennedy L, Lanoue L, Lantier L, Macy J, Malabanan E, McGuinness O, Perry R, Port D, Qi N, Elias C, Shulman G, Wasserman D, Lloyd K. The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity. Mammalian Genome 2024, 35: 485-496. PMID: 39191872, PMCID: PMC11522164, DOI: 10.1007/s00335-024-10067-y.Peer-Reviewed Original ResearchMouse Metabolic Phenotyping CentersMouse model of diabetesModels of diabetesNational Institutes of HealthNational Institute for DiabetesDigestive and Kidney DiseasesBehavioral phenotyping testsRenal functionProcedure in vivoFood intakeIn vivo characterizationMouse modelHeterogeneity of diabetesKidney diseaseBody compositionPhenotyping CentersInstitutes of HealthMiceObesityDiabetesPhenotypic testsWhole-body carbohydrateInsulin actionLipid metabolismLiving miceSmall molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease
Gaspar R, Sakuma I, Nasiri A, Hubbard B, LaMoia T, Leitner B, Tep S, Xi Y, Green E, Ullman J, Petersen K, Shulman G. Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease. AJP Endocrinology And Metabolism 2024, 327: e524-e532. PMID: 39171753, PMCID: PMC11482269, DOI: 10.1152/ajpendo.00175.2024.Peer-Reviewed Original ResearchGAA-KO miceMouse model of Pompe diseaseModel of Pompe diseasePompe diseaseMetabolic dysregulationRegular chowMouse modelSmall molecule inhibitionInsulin sensitivityReduced spontaneous activityGroups of male miceEnzyme acid alpha-glucosidaseProgressive muscle weaknessImprove metabolic dysregulationSynthase IWhole-body insulin sensitivityAcid alpha-glucosidaseImproved glucose toleranceIncreased AMPK phosphorylationWT miceAbnormal accumulation of glycogenGlycogen storage disorderMale miceSpontaneous activityImproved biomarkersCytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipolysis, and gluconeogenesis via CAMKII activation
LaMoia T, Hubbard B, Guerra M, Nasiri A, Sakuma I, Kahn M, Zhang D, Goodman R, Nathanson M, Sancak Y, Perelis M, Mootha V, Shulman G. Cytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipolysis, and gluconeogenesis via CAMKII activation. Cell Metabolism 2024, 36: 2329-2340.e4. PMID: 39153480, PMCID: PMC11446666, DOI: 10.1016/j.cmet.2024.07.016.Peer-Reviewed Original Research292-OR: Coenzyme A Synthase Knockdown Alleviates Metabolic Dysfunction–Associated Steatohepatitis via Decreasing Cholesterol in Liver Lipid Droplets
SAKUMA I, GASPAR R, NASIRI A, KAHN M, GUERRA M, YIMLAMAI D, MURRAY S, PERELIS M, BARNES W, VATNER D, PETERSEN K, SAMUEL V, SHULMAN G. 292-OR: Coenzyme A Synthase Knockdown Alleviates Metabolic Dysfunction–Associated Steatohepatitis via Decreasing Cholesterol in Liver Lipid Droplets. Diabetes 2024, 73 DOI: 10.2337/db24-292-or.Peer-Reviewed Original ResearchCholine-deficient l-amino acid-defined high-fat dietAccumulation of cholesterolMRNA expressionPlasma ALTL-amino acid-defined high-fat dietProtective effectLiver lipid dropletsType 2 diabetesPotential therapeutic approachHigh-fat dietDecreased plasma ALTFibrosis markersFree cholesterol accumulationLipid dropletsLiver inflammationDay 1Macrophage markersHepatic inflammationMouse modelMarker expressionTherapeutic approachesDay 2Day 3Day 7Fibrosis
2023
1558-P: The Mitochondrial Calcium Uniporter Regulates Hepatic Mitochondrial Oxidation and Intracellular Redox In Vivo
LAMOIA T, HUBBARD B, GUERRA M, GOODMAN R, NATHANSON M, SHULMAN G. 1558-P: The Mitochondrial Calcium Uniporter Regulates Hepatic Mitochondrial Oxidation and Intracellular Redox In Vivo. Diabetes 2023, 72 DOI: 10.2337/db23-1558-p.Peer-Reviewed Original ResearchNonalcoholic fatty liver diseaseHepatic mitochondrial oxidationMitochondrial calcium uniporterHepatocellular redox stateFatty liver diseaseEctopic lipid accumulationType 2 diabetesHepatic lipid contentNovel therapeutic targetMitochondrial oxidationHepatic triacylglycerol contentMitochondrial calcium influxMitochondrial redox ratioMitochondrial calciumKnockout mouse modelFortress BiotechMitochondrial fat oxidationNonalcoholic steatohepatitisLiver diseaseWT miceKO miceMetabolic dysfunctionCalcium uniporterCalcium influxMouse modelInhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis
Luukkonen P, Sakuma I, Gaspar R, Mooring M, Nasiri A, Kahn M, Zhang X, Zhang D, Sammalkorpi H, Penttilä A, Orho-Melander M, Arola J, Juuti A, Zhang X, Yimlamai D, Yki-Järvinen H, Petersen K, Shulman G. Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2217543120. PMID: 36669104, PMCID: PMC9942818, DOI: 10.1073/pnas.2217543120.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseLiver fibrosisLiver diseaseCommon chronic liver diseaseChronic liver diseaseFatty liver diseaseRisk of fibrosisDistinct mouse modelsPyrimidine catabolismNonalcoholic steatohepatitisMouse modelTherapeutic targetFibrosisDihydropyrimidine dehydrogenaseHuman liverA variantCommon variantsMetabolomics approachDiseaseMiceInhibitionCatabolismKnockdownSteatohepatitisGimeracil
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 roleImmunotherapyMorbidityIsthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis
Jiang Z, Zhao M, Voilquin L, Jung Y, Aikio MA, Sahai T, Dou FY, Roche AM, Carcamo-Orive I, Knowles JW, Wabitsch M, Appel EA, Maikawa CL, Camporez JP, Shulman GI, Tsai L, Rosen ED, Gardner CD, Spiegelman BM, Svensson KJ. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Cell Metabolism 2021, 33: 1836-1852.e11. PMID: 34348115, PMCID: PMC8429235, DOI: 10.1016/j.cmet.2021.07.010.Peer-Reviewed Original ResearchConceptsFatty liver diseaseAdipose glucose uptakeGlucose toleranceLiver diseaseHepatic steatosisGlucose uptakeDiet-induced obese miceImpaired glucose toleranceInsulin-like growth factor receptorType 2 diabetesHepatic lipid synthesisIsthmin 1Growth factor receptorObese miceInsulin sensitivityTherapeutic dosingMouse modelGlucoregulatory functionGlucose regulationUnmet needTherapeutic potentialDiabetesLipid accumulationPI3K-AktFactor receptor
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
2014
Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis
Perry RJ, Zhang XM, Zhang D, Kumashiro N, Camporez JP, Cline GW, Rothman DL, Shulman GI. Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nature Medicine 2014, 20: 759-763. PMID: 24929951, PMCID: PMC4344321, DOI: 10.1038/nm.3579.Peer-Reviewed Original Research
2010
Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice
Ayala JE, Consortium F, Samuel V, Morton G, Obici S, Croniger C, Shulman G, Wasserman D, McGuinness O. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Disease Models & Mechanisms 2010, 3: 525-534. PMID: 20713647, PMCID: PMC2938392, DOI: 10.1242/dmm.006239.Peer-Reviewed Original Research