2022
Ethnic and gender differences in hepatic lipid content and related cardiometabolic parameters in lean individuals
Petersen KF, Dufour S, Li F, Rothman DL, Shulman GI. Ethnic and gender differences in hepatic lipid content and related cardiometabolic parameters in lean individuals. JCI Insight 2022, 7 PMID: 35167495, PMCID: PMC9057590, DOI: 10.1172/jci.insight.157906.Peer-Reviewed Original ResearchConceptsCardiometabolic risk factorsInsulin resistanceRisk factorsHDL cholesterolLDL cholesterolTotal cholesterolLean individualsMatsuda insulin sensitivity indexAI menCardiovascular risk factorsHomeostatic model assessmentHepatic triglyceride contentInsulin sensitivity indexType 2 diabetesHepatic lipid contentNovo Nordisk FoundationUric acid concentrationCardiometabolic parametersCardiovascular riskPremenopausal womenFatty liverPlasma insulinInsulin sensitivityPlasma concentrationsModel assessment
2020
459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome
GOEDEKE L, ROTLLAN N, TOUSSAINT K, NASIRI A, ZHANG X, LEE J, ZHANG X, FERNÁNDEZ-HERNANDO C, SHULMAN G. 459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome. Diabetes 2020, 69 DOI: 10.2337/db20-459-p.Peer-Reviewed Original ResearchWhole-body insulin sensitivitySpouse/partnerInsulin sensitivityCardiovascular diseaseMetabolic syndromeAortic root plaque areaHigh fat-cholesterol dietLdlr-/- mouse modelTreatment of CVDEctopic lipid contentLDLR-/- micePeripheral insulin sensitivityNecrotic core areaType 2 diabetesAnti-atherogenic roleFibrous cap areaAdvisory PanelCRMP treatmentAttenuates AtherosclerosisCardiometabolic disordersFatty liverCholesterol dietInsulin resistanceNondiabetic individualsHepatic triglycerides
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
2013
Reversal of Hypertriglyceridemia, Fatty Liver Disease, and Insulin Resistance by a Liver-Targeted Mitochondrial Uncoupler
Perry RJ, Kim T, Zhang XM, Lee HY, Pesta D, Popov VB, Zhang D, Rahimi Y, Jurczak MJ, Cline GW, Spiegel DA, Shulman GI. Reversal of Hypertriglyceridemia, Fatty Liver Disease, and Insulin Resistance by a Liver-Targeted Mitochondrial Uncoupler. Cell Metabolism 2013, 18: 740-748. PMID: 24206666, PMCID: PMC4104686, DOI: 10.1016/j.cmet.2013.10.004.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseFatty liver diseaseInsulin resistanceLiver diseaseMetabolic syndromeFatty liverSystemic toxicityWhole-body insulin resistanceMajor predisposing conditionReversal of hypertriglyceridemiaTreatment of hypertriglyceridemiaType 2 diabetesMuscle insulin resistanceWide therapeutic indexPredisposing conditionRat modelProtein kinase C epsilonHypertriglyceridemiaTherapeutic indexFed ratsBeneficial effectsLiverPKCθ activitySyndromeMitochondrial uncoupler