Extracellular vesicles (EVs) have emerged as important mediators of intertissue signaling and exercise adaptations. In this human study, we provide evidence that muscle-specific microRNA-1 (miR-1) was transferred to adipose tissue via EVs following an acute bout of resistance exercise. Using a multimodel machine learning automation tool, we discovered muscle primary miR-1 transcript and CD63 ⁺ EV count in circulation as top explanatory features for changes in adipose miR-1 levels in response to resistance exercise. RNA-Seq and in-silico prediction of miR-1 target genes identified caveolin 2 ( CAV2 ) and tripartite motif containing 6 ( TRIM6 ) as miR-1 target genes downregulated in the adipose tissue of a subset of participants with the highest increases in miR-1 levels following resistance exercise. Overexpression of miR-1 in differentiated human adipocyte-derived stem cells downregulated these miR-1 targets and enhanced catecholamine-induced lipolysis. These data identify a potential EV-mediated mechanism by which skeletal muscle communicates with adipose tissue and modulates lipolysis via miR-1.

Caffeine is often used in a variety of forms to enhance athletic performance; however, research regarding caffeine’s effects on strength and power in female athletes is lacking. Therefore, the purpose of this study was to analyze the acute effects of caffeine anhydrous (6 mg/kg of body mass) on jumping performance and maximal strength in female collegiate athletes. Eleven athletes (19.7 ± 0.9 yrs; 166.4 ± 10.2 cm, 67.7 ± 9.4 kg) performed two testing sessions separated by one week, and randomly received caffeine or placebo using a double-blind approach. Heart rate, blood pressure, and tympanic temperature were recorded before athletes received each condition, following 60 min of quiet sitting, and directly after performance testing. Athletes were assessed on unweighted and weighted squat jump height (SJH0, SJH20) and countermovement jump height (CMJH0, CMJH20), isometric mid-thigh pull peak force (IPF), and rate of force development from 0–200 ms (RFD200). Resting systolic blood pressure was significantly greater following caffeine administration compared to a placebo (p = 0.017). There were small, significant differences in SJH0 (p = 0.035, g = 0.35), SJH20 (p = 0.002, g = 0.49), CMJH0 (p = 0.015, g = 0.19), and CMJH20 (p < 0.001, g = 0.37) in favor of caffeine over placebo. However, there was no significant difference in IPF (p = 0.369, g = 0.12) and RFD200 (p = 0.235, g = 0.32) between conditions. Therefore, caffeine appears to enhance jumping performance, but not maximal strength in female collegiate athletes.

Roberts et al. have provided an insightful counterpoint to our review article on the utility of the synergist ablation model. The purpose of this review is to provide some further dialogue regarding the strengths and weaknesses of the synergist ablation model. Specifically, we highlight that the robustness of the model overshadows surgical limitations. We also compare the transcriptomic responses to synergist ablation in mice and resistance exercise in humans to identify common pathways. We conclude that “cell growth is cell growth” and that the mechanisms available to cells to accumulate biomass and increase in size are similar across cell types and independent of the rate of growth.

Skeletal muscle exhibits remarkable plasticity to adapt to stimuli such as mechanical loading. The mechanisms that regulate skeletal muscle hypertrophy due to mechanical overload have been thoroughly studied. Remarkably, our understanding of many of the molecular and cellular mechanisms that regulate hypertrophic growth were first identified using the rodent synergist ablation (SA) model and subsequently corroborated in human resistance exercise training studies. To demonstrate the utility of the SA model, we briefly summarize the hypertrophic mechanisms identified using the model and the following translation of these mechanism to human skeletal muscle hypertrophy induced by resistance exercise training.

Burke, BI, Carroll, KM, Travis, SK, Stone, ME, and Stone, MH. Two days versus four days of training cessation following a step-taper in powerlifters. J Strength Cond Res 37(12): e625–e632, 2023—Tapering and training cessation are methods of training load management aimed at optimizing athlete preparedness leading into competition. Such practices are often used by strength sport athletes such as powerlifters (i.e., athletes who compete in the back squat [BS], bench press [BP], and deadlift [DL]). The purpose of this study was to compare the differences in maximal strength, subjective recovery and stress state, and body composition alterations in strength athletes undergoing a 1-week step-taper followed by either a 2-day (2D) or 4-day (4D) period of training cessation. Twelve powerlifters (22.3 ± 2.1 yrs; 92.1 ± 20.4 kg; 174.8 ± 7.5 cm) completed a 6-week training protocol aimed at peaking 1 repetition maximum (1RM) strength on BS, BP, and DL. Body composition, subjective recovery and stress state, and 1RM on BS, BP, and DL were assessed before an overreach week (T1) and after the periods of training cessation (T2) for each group. Alpha criterion was set at p ≤ 0.05. There were significant increases in BP (p = 0.032, g = 0.10), powerlifting total (p = 0.014, g = 0.11), and DOTS score (p = 0.006, g = 0.12) after 2D of cessation. However, after 4D of cessation, significant increases were only observed in DL (p = 0.019, g = 0.11) along with significant decreases in BP (p = 0.003, g = −0.13). There were no statistically significant changes in any other variable for either group indicating that BS, psychometric, and body composition data were maintained between T1 and T2. The results of this study support the use of 1-week step-tapers, followed by a short period of training cessation (2–4D) to maintain or improve maximal strength performance.

We previously reported that skeletal muscle adaptation to regular exercise requires a healthy gut microbiome, contributing to growing evidence that some exercise benefits are mediated by microbiome-derived metabolites. Here, to identify such exercise-associated microbial metabolites, we transfer cecal contents from exercise-trained female donor mice into exercise-naïve female recipient mice undergoing unilateral hindlimb immobilization. Recipients of cecal material from exercise-trained donors exhibit less muscle atrophy compared with those receiving transfers from sedentary donors. Untargeted metabolomics reveal metabolites enriched in cecal content, serum, and muscle of recipients from exercise-trained donors, consistent with microbial origin. Oral administration of two such metabolites (pipecolic acid and succinate) attenuates muscle atrophy and preserves muscle function in exercise-naïve mice, potentially by enhancing cellular energy status and translational capacity. These findings further define the gut microbiome-skeletal muscle axis and provide evidence that exercise-associated microbial metabolites serve as a novel class of exercise mimetics for treating conditions responsive to physical activity.