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.

Assessment of Vascular Function in Response to High-Fat and Low-Fat Ground Beef Consumption in Men.

Red meat is stigmatized as an unhealthy protein choice; however, its impacts on vascular function have not been evaluated. We aimed to measure the vascular impact of adding either low-fat (~5% fat) ground beef (LFB) or high-fat (~25% fat) ground beef (HFB) to a habitual diet in free-living men. Twenty-three males (39.9 ± 10.8 years, 177.5 ± 6.7 cm, 97.3 ± 25.0 kg) participated in this double-blind crossover study. Assessment of vascular function and aerobic capacity were measured at entry and in the last week of each intervention and washout period. Participants then completed two 5-week dietary interventions (LFB or HFB; 5 patties/week) in a randomized order with a 4-week washout. Data were analyzed via 2 × 2 repeated-measures ANOVA (p < 0.05). The HFB intervention improved FMD relative to all other time points, while lowering systolic (SBP) and diastolic blood pressure (DBP) relative to entry. Neither the HFB nor the LFB altered pulse wave velocity. The addition of either low- or high-fat ground beef did not negatively alter vascular function. In fact, consuming HFB improved FMD and BP values, which may be mediated by lowering LDL-C concentrations.

Predicting muscular strength using demographics, skeletal dimensions, and body composition measures.

The purpose of this study was to develop an equation to predict strength for seven common resistance training exercises using anthropometric and demographic measures. One-hundred forty-seven healthy adults (74 males, 73 females, 35 ±â€¯12 yr, 174 ±â€¯10 cm, 88 ±â€¯19 kg) volunteered to participate. Body composition values (regional/total) and body dimensions were assessed using dual-energy x-ray absorptiometry (DEXA). Subjects underwent the following maximal strength assessments: Leg Press, Chest Press, Leg Curl, Lat Pulldown, Leg Extension, Triceps Pushdown, and Biceps Curl. Multiple linear regression with stepwise removal was used to determine the best model to predict maximal strength for each exercise. Independent predictor variables identified (p < 0.05) were height (cm); weight (kg); BMI; age; sex (0 = F,1 = M); regional lean masses (LM,kg); fat mass (FM,kg); fat free mass (FFM,kg); percent fat (%BF); arm, leg, and trunk lengths (AL, LL, TL; cm); and shoulder width (SW,cm). Analyses were performed with and without regional measures to accommodate scenarios where DEXA is unavailable. All models presented were significant (p < 0.05, R 2 = 0.68-0.83), with regional models producing the greatest accuracy. Results indicate that maximal strength for individual resistance exercises can be reasonably estimated in adults.

Effects of an Acute Strength and Conditioning Training Session on Dual-Energy X-Ray Absorptiometry Results.

Lytle, JR, Stanelle, ST, Kravits, DM, Ellsworth, RL, Martin, SE, Green, JS, and Crouse, SF. Effects of an acute strength and conditioning training session on dual-energy x-ray absorptiometry results. J Strength Cond Res 34(4): 901-904, 2020-The purpose of this study was to determine whether an athletic strength and conditioning (S&C) session will alter body composition estimates of a dual-energy x-ray absorptiometry (DXA) scan. Twenty-two strength-trained individuals (15 men, 7 women, 24 ± 2 years, 174.2 ± 8.5 cm, 83.5 ± 15.0 kg) volunteered to participate in the study. Each subject underwent 2 DXA scans, before and after completion of the S&C session, which consisted of upper- and lower-body resistance exercises and interval running. Subjects consumed a free-living meal before the first scan, after which only ad libitum water intake was consumed until completing the second scan. Results were analyzed through sex by time repeated-measures analysis of variance. If no interaction effect was observed, results were next analyzed through correlated t-test (α = 0.05). Significant sex by time interactions were observed for arm total and lean mass, as well as a significant main effect of time showing a decrease in arm lean mass after the S&C session. Values before and after the S&C session that resulted in significant differences via correlated t-test are displayed in Table 1. Results revealed a significant decrease in total mass, arm and leg percent fat, and trunk lean mass, and an increase in leg lean mass.

One Week of L-Citrulline Supplementation Improves Performance in Trained Cyclists.

Stanelle, ST, McLaughlin, KL, and Crouse, SF. One week of L-citrulline supplementation improves performance in trained cyclists. J Strength Cond Res 34(3): 647-652, 2020-L-citrulline (CIT) is a nonessential amino acid that is touted as an ergogenic aid for athletic performance because of its purported ability to stimulate nitric oxide production. Although previous research has demonstrated that CIT supplementation over a period of days improves physiological factors such as V[Combining Dot Above]O2 kinetics, no studies to date have explored whether there is a direct benefit to endurance performance. This study used a randomized, double-blind, crossover design to test whether chronic supplementation with pure CIT improves cycling performance over a maltodextrin placebo (PLAC). Nine trained male cyclists (24 ± 3 years; 181 ± 7 cm; 76 ± 13 kg; 4.18 ± 0.51 L·min V[Combining Dot Above]O2max) completed two 7-day supplementation periods (6 g·d of CIT or PLAC) separated by a 7-day washout. Subjects consumed the final 6-g dose 2 hours before the cycling performance evaluation, which consisted of a 40-km time trial (TT) followed by a supramaximal sprint repeat task (SRT). Paired t-tests and repeated-measures analysis of variance (α = 0.05) were used to analyze TT and SRT data, respectively. CIT supplementation produced an improvement in TT time of 5.2% that trended toward significance (p = 0.08). Furthermore, CIT promoted a significant increase in average heart rate, average rating of perceived exertion, and average power throughout the TT (p < 0.05). However, supplementation with CIT did not prevent fatigue during the SRT. Overall, this study is the first to demonstrate that CIT supplementation may provide a modest improvement to endurance cycling performance in trained athletes.