Genetically increasing flux through β-oxidation in skeletal muscle increases mitochondrial reductive stress and glucose intolerance
Cody D. Smith, Chien‐Te Lin, Shawna L. McMillin, Luke A. Weyrauch, Cameron A. Schmidt, Cheryl A. Smith, Irwin J. Kurland, Carol A. Witczak, P. Darrell Neufer
Abstract
Prior work has suggested that mitochondrial dysfunction is an underlying cause of insulin resistance in muscle because it limits fatty acid oxidation and therefore leads to the accumulation of cytotoxic lipid intermediates. The implication has been that therapeutic strategies to accelerate β-oxidation will be protective. The current study provides evidence that genetically increasing flux through β-oxidation in muscle imposes reductive stress that is not beneficial but rather detrimental to metabolic regulation.
Topics & Concepts
Internal medicineEndocrinologyBeta oxidationSkeletal musclePeroxisomeLipid oxidationMitochondrionBiologyOxidative stressCarbohydrate metabolismInsulin resistanceCatalaseChemistryBiochemistryMetabolismInsulinReceptorAntioxidantMedicineAdipose Tissue and MetabolismMitochondrial Function and PathologyMuscle metabolism and nutrition