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
2022
Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance
Huang Y, Zhou JH, Zhang H, Canfrán-Duque A, Singh AK, Perry RJ, Shulman G, Fernandez-Hernando C, Min W. Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. Journal Of Clinical Investigation 2022, 132 PMID: 35202005, PMCID: PMC9057632, DOI: 10.1172/jci148852.Peer-Reviewed Original ResearchConceptsBrown adipose tissueBAT inflammationInsulin resistanceMitochondrial reactive oxygen speciesReactive oxygen speciesAberrant innate immune responsesDiet-induced insulin resistanceSystematic metabolismDiet-induced obesityNLRP3 inflammasome pathwayWhole-body energy metabolismCGAS/STINGInnate immune responseFatty acid oxidationExcessive mitochondrial reactive oxygen speciesMetabolic benefitsImmune responseInflammasome pathwayAdipose tissueInflammationInhibition reversesLipid uptakeLipid metabolismThioredoxin 2Adaptive thermogenesis