Abstract
Abstract only Background: Increased intramyocellular lipid storage occurs in skeletal muscle of both athletes and type 2 diabetes patients (T2D) but their metabolic phenotypes are at opposite ends of insulin sensitivity and cardiometabolic risk. Hypothesis: Intramyocellular lipid saturation and flux are determinants of insulin resistance. Methods: Age-matched athletes (n=28) and T2D (n=27) underwent 1 H-magnetic resonance spectroscopy for analysis of saturated (fSL) and unsaturated lipid (fUL) fractions of vastus lateralis, blood lipids, glucose and insulin sensitivity, skeletal muscle biopsy for lipidomics/insulin signalling, cardiopulmonary exercise peak VO 2 and intravenous administration of stable isotopes of [U- 13 C]-palmitate and -linoleate for skeletal muscle saturated/unsaturated fatty acid fluxes (fractional synthesis rate, FSR). Tests were performed at baseline and after controlled insulin sensitivity changes (4-week athletes deconditioning and endurance exercise training at ≥65% of baseline peakVO 2, 5 hours/week x 8 weeks in T2D). Results: We demonstrate higher intramyocellular fSL and lower fUL in athletes compared to T2D (p=0.0004). Trained athletes have a 4-fold (palmitate) and 2.2-fold (linoleate) higher FSR compared to T2D (p=0.005 and 0.006, respectively). Athletes’ deconditioning results in reductions in skeletal muscle lipid saturation, palmitate and linoleate FSR. Conversely, 8-week endurance training of T2D results in intramyocellular lipid saturation increase (p<0.0001) as well as a relatively larger (2.2-fold) palmitate FSR increase (p=0.04) than the 1.8-fold linoleate FSR increase (p=0.03), re-aligning the T2D skeletal muscle phenotype to that of deconditioned athletes. These adaptations were synchronous with significant insulin sensitivity improvement (p<0.05), decrease in serum cholesterol (p=0.02) and triglycerides (p=0.0005), improved glycaemic control (HBA1c, p=0.0003), increased peak VO 2 (p<0.0001) and upregulation of skeletal muscle phosphorylated AKT (p=0.01) and AMPK (p=0.005) in T2D. Conclusions: Maladapted intramyocellular lipid storage and fluxes in T2D patients show reversibility after endurance training through increased contributions of the saturated fatty acids pools.