Short-Term Aerobic and Interval Training Improves Muscle Mitochondrial Function and Reveals a New Role for an Old Protein

Abstract

Exercise training has well-documented beneficial effects on skeletal muscle (muscle) mitochondrial function, which can be evaluated from clinical and molecular aspects within the same individual. We evaluated two cohorts at baseline: 1) lean/overweight sedentary (LOS) and 2) lean active (LA), and investigated the effects of three weeks of aerobic training in LOS subjects. All assessments were performed before (PRE) and following (POST) the intervention. In vivo muscle mitochondrial function was assessed by 31P-MRS (ATPmax). Muscle biopsies were performed in the vastus lateralis in the fasted state. Muscle tissue mitochondrial function was quantified via 14C-palmitate oxidation (14C-CO2) assays and high-resolution respirometry (Complex I, Complexes I+II, ETS). Transcriptomic profiles were examined by microarrays combined with in-depth bioinformatics analyses and validated via qRT-PCR. Fiber type and mitochondrial (mt)DNA copy number were quantified via immunohistochemistry and qPCR, respectively. LA subjects had significantly higher VO2peak and muscle mitochondrial function in vivo and in tissue vs. LOS PRE. Three weeks of aerobic training significantly improved muscle mitochondrial function in vivo and in tissue in LOS subjects [to the level of LA subjects] without affecting VO2peak, fiber type nor mitochondrial content. Global transcriptomic analyses revealed downregulation of Tribbles 1 in LOS PRE vs. LA that was confirmed by qRT-PCR in LOS PRE vs. LA. Tribbles 1 mRNA was significantly reduced with training (LOS PRE vs. POST) and inversely related with muscle tissue mitochondrial respiration. Our data identified a novel target related to exercise-induced improvements in muscle mitochondrial function and highlight a potential new role for Tribbles 1 in muscle oxidative capacity. Disclosure S. Parsons: None. M.F. Pino: None. A.P. Hodges: None. F. Yi: None. E.A. Carnero: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc.. S.R. Smith: None. L.M. Sparks: None.