Author(s): ALOTHMAN, S., JAMESON, T., KILROE, S., WALL, B., STEPHENS, F. , Institution: PRINCESS NOURAH BINT ABDULRAHMAN UNIVERSITY, Country: SAUDI ARABIA, Abstract-ID: 2284

INTRODUCTION:
Human models of muscle disuse are associated with muscle atrophy, insulin resistance of carbohydrate metabolism, and lipid accumulation. However, in practice, muscle disuse is often preceded by injury or trauma causing an inflammatory response. The aim of the present study was to characterize the changes in expression of skeletal muscle genes associated with inflammation and carbohydrate and lipid metabolism in a ‘complex’ human muscle disuse model that has been preceded by muscle damaging exercise.
METHODS:
Twenty-one healthy males (20±1yr, BMI 24±1 kg/m2) completed a 7-day period of knee immobilization that either proceeded by no exercise (CON; n=11) or a bout of 300 bilateral and maximal eccentric muscle contractions (DAM;n=10) immediately before immobilization. At days 0, 2, and 7 muscle biopsies were obtained. Muscle mRNA expression of 12 genes that encode inflammatory proteins known to respond to damaging exercise, and proteins that are rate limiting steps in muscle carbohydrate and lipid metabolism, was determined by Real-Time PCR. Muscle mRNA expression was calculated using the 2-ΔΔCT method, with the log2 fold change in mRNA abundance calculated relative to the non-immobilized leg at day 0 for each participant. The study was approved by the Sport and Health Sciences Ethics Committee of the University of Exeter (171206/B/08). Data were analysed using repeated-measure two-factor ANOVA tests [with condition (CON vs. DAM) and time as within-participant factors.
RESULTS:
Immobilization increased expression of the inflammation related genes monocyte chemoattractant protein 2 (CCL8), interleukin 18 (IL18), and a tumor necrosis factor alpha receptor (TNFRSF12A) in both groups after 7 days (P<0.01), whereas an interleukin 1 receptor (Il1RL1) did not change. Prior eccentric exercise in DAM resulted in greater upregulation of IL18 (P<0.05) and TNFRSF12A (P<0.05) at day 2. Carbohydrate metabolism associated genes for pyruvate dehydrogenase 4 (PDK4) showed upregulation earlier at day 2 of immobilisation in DAM (P<0.01) compared to D7 in CON (P<0.05), while both glycogen phosphorylase (PYGM) and lactate dehydrogenase (LDHA) genes were downregulated in response to immobilization similarly in both groups (P<0.05). No significant change was observed in hexokinase 2 (HK2) expression. The expression of genes associated with fat oxidation (HADHB, ACAT1, and CPT1B) was decreased (P<0.05), and a gene associated with lipid storage (PNPLA2) was increased (P<0.05), to a similar degree in both groups after 7 days.
CONCLUSION:
Observed changes in genes expression involved in fat and carbohydrate metabolism after immobilisation are consistent with a decrease in oxidation expected with reduced energy demand. Damaging eccentric exercise induced an inflammatory response after 2 days of immobilisation that was associated with a pattern of earlier reduction in carbohydrate (PDK4), but not fat oxidation, suggesting that inflammation may exacerbate the insulin resistance of physical inactivity.