2023
1569-P: Lysophosphatidic Acid Mediates Inflammation in Liver and White Adipose Tissue in a Rat Model of 1-acyl-sn-glycerol-3-phosphate Acyltransferase 2 Deficiency
SAKUMA I, GASPAR R, LUUKKONEN P, KAHN M, MURRAY S, SAMUEL V, PETERSEN K, SHULMAN G. 1569-P: Lysophosphatidic Acid Mediates Inflammation in Liver and White Adipose Tissue in a Rat Model of 1-acyl-sn-glycerol-3-phosphate Acyltransferase 2 Deficiency. Diabetes 2023, 72 DOI: 10.2337/db23-1569-p.Peer-Reviewed Original ResearchWhite adipose tissueControlled-release mitochondrial protonophoreCongenital generalized lipodystrophyAGPAT2 deficiencyHepatic inflammationASO treatmentAdipose tissueLysophosphatidic acidAdult male SD ratsAntisense oligonucleotideMale SD ratsNovel therapeutic targetNovo NordiskCRMP treatmentFortress BiotechWAT inflammationDohme Corp.SD ratsRat modelAGPAT2 geneGeneralized lipodystrophyInflammationTherapeutic targetIonis PharmaceuticalsDeficient animals
2022
Sex‐ and strain‐specific effects of mitochondrial uncoupling on age‐related metabolic diseases in high‐fat diet‐fed mice
Goedeke L, Murt KN, Di Francesco A, Camporez JP, Nasiri AR, Wang Y, Zhang X, Cline GW, de Cabo R, Shulman GI. Sex‐ and strain‐specific effects of mitochondrial uncoupling on age‐related metabolic diseases in high‐fat diet‐fed mice. Aging Cell 2022, 21: e13539. PMID: 35088525, PMCID: PMC8844126, DOI: 10.1111/acel.13539.Peer-Reviewed Original ResearchConceptsControlled-release mitochondrial protonophoreAge-related metabolic diseasesHepatocellular carcinomaMetabolic diseasesHigh-fat diet-fed miceProtein kinase C epsilon activationDiet-induced obese miceWhole-body energy expenditureC57BL/6J male miceDiet-fed miceHigh-fat dietHepatic lipid peroxidationHepatic lipid contentMitochondrial uncouplingHepatic insulin resistanceHigh therapeutic indexHepatic mitochondrial biogenesisStrain-specific effectsSex-specific mannerCRMP treatmentHFD feedingUnwanted side effectsObese miceInsulin resistanceChronic ingestion
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