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
2019
Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates
Goedeke L, Peng L, Montalvo-Romeral V, Butrico GM, Dufour S, Zhang XM, Perry RJ, Cline GW, Kievit P, Chng K, Petersen KF, Shulman GI. Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates. Science Translational Medicine 2019, 11 PMID: 31578240, PMCID: PMC6996238, DOI: 10.1126/scitranslmed.aay0284.Peer-Reviewed Original ResearchConceptsControlled-release mitochondrial protonophoreNonalcoholic fatty liver diseaseCRMP treatmentHepatic triglyceridesDiet-induced rodent modelReversal of hypertriglyceridemiaFatty liver diseaseNonhuman primate modelMitochondrial protonophoreEndogenous glucose productionLow-density lipoproteinMitochondrial fat oxidationHepatic inflammationMetabolic syndromeFatty liverLiver diseaseHepatic steatosisInsulin resistanceAdverse reactionsPlasma triglyceridesPrimate modelOral administrationFood intakeHepatic mitochondrial oxidationRodent models19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates
GOEDEKE L, ROMERAL V, BUTRICO G, KAHN M, DUFOUR S, ZHANG X, CLINE G, PETERSEN K, CHNG K, SHULMAN G. 19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates. Diabetes 2019, 68 DOI: 10.2337/db19-19-or.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreSpouse/partnerCRMP treatmentInsulin resistanceDiet-induced rodent modelJanssen ResearchReversal of hypertriglyceridemiaNAFLD/NASHInflammation/fibrosisNonhuman primate modelMitochondrial protonophoreEndogenous glucose productionHepatic insulin resistanceHepatic acetyl-CoA contentAdvisory PanelMitochondrial fat oxidationMetabolic syndromeFatty liverHepatic steatosisAdverse reactionsHepatic triglyceridesAcetyl-CoA contentPrimate modelNovo Nordisk A/S.Food intake
2018
Effect of a Controlled-Release Mitochondrial Protonophore (CRMP) on Healthspan and Lifespan in Mice
GOEDEKE L, CAMPOREZ J, NASIRI A, WANG Y, ZHANG X, SHULMAN G. Effect of a Controlled-Release Mitochondrial Protonophore (CRMP) on Healthspan and Lifespan in Mice. Diabetes 2018, 67 DOI: 10.2337/db18-123-lb.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreCRMP treatmentHepatic steatosisDiet-induced rodent modelWhole body insulin responsivenessInflammation/fibrosisMale C57BL/6J miceWhole-body energy expenditureHyperinsulinemic-euglycemic clampHigh-fat dietType 2 diabetesGlucose infusion rateMitochondrial protonophorePlasma glucose concentrationWide therapeutic indexStrict dietary regimeSecond-generation compoundsTransaminase levelsFatty liverLiver triglyceridesInsulin resistanceAge-related diseasesC57BL/6J miceHepatic triglyceridesFood intake
2016
Mitochondrial Protonophores For Treatment of NAFLD/NASH and Type 2 Diabetes
Shulman G. Mitochondrial Protonophores For Treatment of NAFLD/NASH and Type 2 Diabetes. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.257.2.Peer-Reviewed Original ResearchType 2 diabetesInsulin resistanceLipid-induced insulin resistanceNAFLD/NASHSkeletal muscleAdipose tissue inflammationEctopic lipid depositionNon-alcoholic steatohepatitisAmerican Diabetes AssociationEctopic lipid depositsAlcoholic steatohepatitisDiabetes AssociationTissue inflammationRecent studiesLipid depositionType 2Lipid depositsHepatic gluconeogenesisCellular mechanismsMitochondrial protonophoreDiabetesMitochondrial inefficiencyLiverMuscleMolecular triggers