The Transcription Factor Mohawk Facilitates Skeletal Muscle Repair via Modulation of the Inflammatory Environment.

Efficient repair of skeletal muscle relies upon the precise coordination of cells between the satellite cell niche and innate immune cells that are recruited to the site of injury. The expression of pro-inflammatory cytokines and chemokines such as TNFα, IFNγ, CXCL1, and CCL2, by muscle and tissue resident immune cells recruits neutrophils and M1 macrophages to the injury and activates satellite cells. These signal cascades lead to highly integrated temporal and spatial control of muscle repair. Despite the therapeutic potential of these factors for improving tissue regeneration after traumatic and chronic injuries, their transcriptional regulation is not well understood. The transcription factor Mohawk (Mkx) functions as a repressor of myogenic differentiation and regulates fiber type specification. Embryonically, Mkx is expressed in all progenitor cells of the musculoskeletal system and is expressed in human and mouse myeloid lineage cells. An analysis of mice deficient for Mkx revealed a delay in postnatal muscle repair characterized by impaired clearance of necrotic fibers and smaller newly regenerated fibers. Further, there was a delay in the expression of inflammatory signals such as Ccl2, Ifnγ, and Tgfß. This was coupled with impaired recruitment of pro-inflammatory macrophages to the site of muscle damage. These studies demonstrate that Mkx plays a critical role in adult skeletal muscle repair that is mediated through the initial activation of the inflammatory response.

Intermittent Energy Restriction Attenuates the Loss of Fat Free Mass in Resistance Trained Individuals. A Randomized Controlled Trial.

There is a lack of research into how lean, resistance trained (RT) individuals respond to intermittent energy restricted diets. Therefore, we investigated body composition changes in RT-individuals during continuous energy restriction or intermittent restriction. A total of 27 males and females (25 ± 6.1 years; 169 ± 9.4 cm; 80 ± 15.6 kg) were randomized to a ~25% caloric restricted diet Refeed (RF; n = 13) or Continuous group (CN; n = 14) in conjunction with 4-days/week resistance training for 7-weeks. RF implemented two consecutive days of elevated carbohydrate (CHO) intake, followed by 5-days of caloric restriction each week. CN adhered to a continuous 7-week caloric restriction. Body mass (BM), fat mass (FM), fat-free mass (FFM), dry fat-free mass (dFFM), and resting metabolic rate (RMR) were assessed pre/post-diet. Both groups significantly reduced BM (RF: baseline = 76.4 ± 15.6 kg, post-diet = 73.2 ± 13.8 kg, Δ3.2 kg; CN: baseline = 83.1 ± 15.4 kg, post-diet = 79.5 ± 15 kg, Δ3.6 kg) and FM (RF: baseline = 16.3 ± 4 kg, post-diet = 13.5 ± 3.6 kg, Δ2.8 kg; CN: baseline = 16.7 ± 4.5 kg, post-diet = 14.4 ± 4.9 kg, Δ2.3 kg) with no differences between groups. FFM (RF: baseline = 60.1 ± 13.8 kg, post-diet = 59.7 ± 13.0 kg, 0.4 kg; CN: baseline = 66.4 ± 15.2 kg, post-diet = 65.1 ± 15.2 kg, Δ1.3 kg p = 0.006), dFFM (RF: baseline = 18.7 ± 5.0 kg, post-diet = 18.5 ± 4.5 kg, Δ0.2 kg; CN: baseline =21.9 ± 5.7 kg, post-diet = 20.0 ± 5.7 kg, Δ1.9 kg), and RMR (RF: baseline = 1703 ± 294, post-diet = 1665 ± 270, Δ38 kcals; CN: baseline = 1867 ± 342, post-diet = 1789 ± 409, Δ78 kcals) were better maintained in the RF group. A 2-day carbohydrate refeed preserves FFM, dryFFM, and RMR during energy restriction compared to continuous energy restriction in RT-individuals.