The autophagy inhibitor NSC185058 suppresses mTORC1-mediated protein anabolism in cultured skeletal muscle.

The mammalian target of rapamycin (mTOR), and specifically the mTOR complex 1 (mTORC1) is the central regulator of anabolism in skeletal muscle. Among the many functions of this kinase complex is the inhibition of the catabolic process of autophagy; however, less work has been done in investigating the role of autophagy in regulating mTORC1 signaling. Using an in vitro model to better understand the pathways involved, we activated mTORC1 by several different means (growth factors, leucine supplementation, or muscle contraction), alone or with the autophagy inhibitor NSC185058. We found that inhibiting autophagy with NSC185058 suppresses mTORC1 activity, preventing any increase in cellular protein anabolism. These decrements were the direct result of action on the mTORC1 kinase, which we demonstrate, for the first time, cannot function when autophagy is inhibited by NSC185058. Our results indicate that, far from being a matter of unidirectional action, the relationship between mTORC1 and the autophagic cascade is more nuanced, with autophagy serving as an mTORC1 input, and mTORC1 inhibition of autophagy as a form of homeostatic feedback to regulate anabolic signaling. Future studies of cellular metabolism will have to consider this fundamental intertwining of protein anabolism and catabolism, and how it ultimately serves to regulate muscle proteostasis.

Certainty of Evidence Assessment in Systematic Reviews Published by High-Impact Sports Science Journals: A Meta-epidemiological Study.

BACKGROUND: Assessing certainty of evidence is a key element of any systematic review. The aim of this meta-epidemiology study was to understand the frequency and ways with which certainty of evidence is assessed in contemporary systematic reviews published in high-impact sports science journals. METHODS: We searched PubMed and relevant journal web sites from 1 August 2016 to 11 October 2022 for systematic reviews published in the top-ten highest-impact journals within the 2020 Journal Citation Report for the Sports Sciences category. Pairs of independent reviewers screened items using a priori established criteria. RESULTS: Of 1250 eligible documents, 258 (20.6%) assessed the certainty of evidence, defined as using two or more distinct domains to provide an overall rating of the trustworthiness of findings across studies. Nine methods were cited for assessing certainty, with the most common being the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach (61.6%). The proportion of systematic reviews assessing certainty of evidence appeared to increase over the 6-year timeframe analyzed. Across all reviews analyzed, a large majority addressed the domains of risk of bias, imprecision, and inconsistency of the results. Other certainty domains including indirectness/applicability were less commonly assessed. DISCUSSION: Only one in five recent contemporary systematic reviews in the field of exercise and sports science assessed certainty of evidence. Organizational and institutional education on methods for assessing evidence may help further increase uptake of these methods and improve both the quality and clinical impact of systematic reviews in the field.

The Effects of Intermittent Diet Breaks during 25% Energy Restriction on Body Composition and Resting Metabolic Rate in Resistance-Trained Females: A Randomized Controlled Trial.

The purpose of this study was to examine the effects of intermittent versus continuous energy restriction on body composition, resting metabolic rate, and eating behaviors in resistance-trained females. Thirty-eight resistance-trained females (mean ± standard deviation age: 22.3 ± 4.2 years) were randomized to receive either six weeks of a continuous 25% reduction in energy intake (n = 18), or one week of energy balance after every two weeks of 25% energy restriction (eight weeks total; n = 20). Participants were instructed to ingest 1.8 g protein/kilogram bodyweight per day and completed three weekly supervised resistance training sessions throughout the intervention. There were no differences between groups for changes over time in body composition, resting metabolic rate, or seven of the eight measured eating behavior variables (p > 0.05). However, a significant group-by-time interaction for disinhibition (p < 0.01) from the Three-Factor Eating Questionnaire was observed, with values (± standard error) in the continuous group increasing from 4.91 ± 0.73 to 6.17 ± 0.71, while values in the intermittent group decreased from 6.80 ± 0.68 to 6.05 ± 0.68. Thus, diet breaks do not appear to induce improvements in body composition or metabolic rate in comparison with continuous energy restriction over six weeks of dieting, but may be employed for those who desire a short-term break from an energy-restricted diet without fear of fat regain. While diet breaks may reduce the impact of prolonged energy restriction on measures of disinhibition, they also require a longer time period that may be less appealing for some individuals.

Sex Differences May Exist for Performance Fatigue but Not Recovery After Single-Joint Upper-Body and Lower-Body Resistance Exercise.

ABSTRACT: Lewis, MH, Siedler, MR, Lamadrid, P, Ford, S, Smith, T, SanFilippo, G, Waddell, B, Trexler, ET, Buckner, S, and Campbell, BI. Sex differences may exist for performance fatigue but not recovery after single-joint upper-body and lower-body resistance exercise. J Strength Cond Res 36(6): 1498-1505, 2022-This study evaluated sex differences in performance recovery and fatigue during dynamic exercise. Twenty-eight resistance-trained males (n = 16) and females (n = 12) completed a repeated-measures, randomized, parallel-groups design. The protocol consisted of a baseline assessment, a recovery period (4, 24, or 48 hours), and a postrecovery assessment. The assessments were identical consisting of 4 sets of 10 repetition maximum (10RM) bicep curls and 4 sets of 10RM leg extensions to failure. Recovery was quantified as the number of total repetitions completed in the postrecovery bout. Fatigue was quantified as the number of repetitions completed set to set within the session. For analysis, we set the level of significance at p ≤ 0.05. No sex differences in performance recovery were observed across any of the investigated time periods for either exercise modality. Regarding fatigue, significant effects were observed for set (p < 0.001) and sex (p = 0.031) for bicep curls. Repetitions dropped in later sets, and females generally completed a greater number of repetitions than males (8.8 ± 0.5 vs. 7.2 ± 0.5). For leg extension, a significant sex × set interaction was observed (p = 0.003), but post hoc tests revealed these sex differences as marginal. Our results suggest that in dynamic bicep curls and leg extensions, other factors unrelated to sex may be more impactful on performance recovery. To optimize an athlete's desired adaptations, it may be more important to consider other variables unrelated to sex such as volume, perceived exertion, and training history when formulating training prescriptions for single-joint exercises.