McMurray 2019 FASEB J
|McMurray F, MacFarlane M, Kim K, Patten DA, Wei-LaPierre L, Fullerton MD, Harper ME (2019) Maternal diet-induced obesity alters muscle mitochondrial function in offspring without changing insulin sensitivity. FASEB J [Epub ahead of print].|
Abstract: In utero overnutrition can predispose offspring to metabolic disease. Although the mechanisms are unclear, increased oxidative stress accelerating cellular aging has been shown to play a role. Mitochondria are the main site of reactive oxygen species (ROS) production in most cell types. Levels of ROS and the risk for oxidative damage are dictated by the balance between ROS production and antioxidant defense mechanisms. Originally considered as toxic species, physiologic levels of ROS are now known to be essential cell signaling molecules. Using a model of maternal overnutrition in C57BL6N mice, we investigate the mechanisms involved in the development of insulin resistance (IR) in muscle. In red and white gastrocnemius muscles of offspring, we are the first to report characteristics of oxidative phosphorylation, H2O2 production, activity of mitoflashes, and electron transport chain supercomplex formation. Results demonstrate altered mitochondrial function with reduced response to glucose in offspring of mice fed a high-fat and high-sucrose diet, increases in mitochondrial leak respiration, and a reduction in ROS production in red gastrocnemius in response to palmitoyl carnitine. We also demonstrate differences in supercomplex formation between red and white gastrocnemius, which may be integral to fiber-type specialization. We conclude that in this model of maternal overnutrition, mitochondrial alterations occur before the development of IR.
Labels: MiParea: Respiration, Developmental biology, Exercise physiology;nutrition;life style Pathology: Diabetes, Obesity Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue Enzyme: Supercomplex
Coupling state: LEAK, OXPHOS Pathway: F, N, S, CIV, ROX HRR: Oxygraph-2k, O2k-Fluorometer
Labels, 2019-10, Amplex UltraRed