Impact of biological sex and sex hormones on molecular signatures of skeletal muscle at rest and in response to distinct exercise training modes.

Substantial divergence in cardio-metabolic risk, muscle size, and performance exists between men and women. Considering the pivotal role of skeletal muscle in human physiology, we investigated and found, based on RNA sequencing (RNA-seq), that differences in the muscle transcriptome between men and women are largely related to testosterone and estradiol and much less related to genes located on the Y chromosome. We demonstrate inherent unique, sex-dependent differences in muscle transcriptional responses to aerobic, resistance, and combined exercise training in young and older cohorts. The hormonal changes with age likely explain age-related differential expression of transcripts. Furthermore, in primary human myotubes we demonstrate the profound but distinct effects of testosterone and estradiol on amino acid incorporation to multiple individual proteins with specific functions. These results clearly highlight the potential of designing exercise programs tailored specifically to men and women and have implications for people who change gender by altering their hormone profile.

Monounsaturated fatty acids protect against palmitate-induced lipoapoptosis in human umbilical vein endothelial cells.

Diets high in saturated fatty acids are linked to increased cardiovascular disease risk, whereas monounsaturated fatty acids have been associated with improved cardiovascular outcomes. Accordingly, cell culture studies have demonstrated that saturated fatty acids, particularly long chain saturated fatty acids such as palmitate, induce dysfunction and cell death in a variety of cell types, and monounsaturated fatty acids may confer protection against palmitate-mediated damage. The aim of the present study was to examine whether monounsaturated fatty acids could protect against palmitate-mediated cell death in endothelial cells, to determine if AMPK inactivation and activation (via compound C and AICAR, respectively) underlies both palmitate-induced damage and monounsaturated fatty acid-mediated protection, and to explore the role of ER stress in this context. Human umbilical vein endothelial cells were examined for cell viability and apoptosis following treatment for 24 hours with palmitate (0.25 and 0.5mM) alone or in combination with the monounsaturated fatty acids oleate or palmitoleate (0.25 and 0.5mM), AICAR, compound C, 4µ8C, or TUDCA. Compared to control cells, palmitate significantly decreased cell viability and increased apoptosis in a dose-dependent manner. The monounsaturated fatty acids oleate and palmitoleate completely prevented the cytotoxic effects of palmitate. Although palmitate induced markers of ER stress, chemical inhibition of ER stress did not prevent palmitate-induced lipoapoptosis. Conversely, the AMPK activator AICAR (0.1 and 0.5mM) conferred protection from palmitate mediated-alterations in viability, apoptosis and ER stress, whereas the AMPK inhibitor compound C (20 and 40µM) significantly exacerbated palmitate-mediated damage. Lastly, co-incubation with palmitate, monounsaturated fatty acids, and compound C significantly mitigated the protective effects of both oleate and palmitoleate. In conclusion, monounsaturated fatty acids confer protection against the cytotoxic effects of palmitate in vascular endothelial cells; and palmitate-mediated damage, as well as monounsaturated-mediated protection, are due in part to inactivation and activation, respectively, of the metabolic regulator AMPK. These results may have implications for understanding the deleterious effects of high saturated fat diets on cardiovascular dysfunction and disease risk.

Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment.

In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m(2); mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 ± 2.7 minutes), methazolamide (+1.4 ± 1.7 minutes), and aminophylline (+1.8 ± 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 ± 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% ± 3% vs. 79% ± 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude.

Total daily energy expenditure is increased following a single bout of sprint interval training.

REGULAR ENDURANCE EXERCISE IS AN EFFECTIVE STRATEGY FOR HEALTHY WEIGHT MAINTENANCE, MEDIATED VIA INCREASED TOTAL DAILY ENERGY EXPENDITURE (TDEE), AND POSSIBLY AN INCREASE IN RESTING METABOLIC RATE (RMR: the single largest component of TDEE). Sprint interval training (SIT) is a low-volume alternative to endurance exercise; however, the utility of SIT for healthy weight maintenance is less clear. In this regard, it is feasible that SIT may evoke a thermogenic response above and beyond the estimates required for prevention of weight gain (i.e., >200-600 kJ). The purpose of these studies was to investigate the hypotheses that a single bout of SIT would increase RMR and/or TDEE. Study 1: RMR (ventilated hood) was determined on four separate occasions in 15 healthy men. Measurements were performed over two pairs of consecutive mornings; each pair was separated by 7 days. Immediately following either the first or third RMR measurement (randomly assigned) subjects completed a single bout of SIT (cycle ergometer exercise). RMR was unaffected by a single bout of SIT (7195 ± 285 kJ/day vs. 7147 ± 222, 7149 ± 246 and 6987 ± 245 kJ/day (mean ± SE); P = 0.12). Study 2: TDEE (whole-room calorimeter) was measured in 12 healthy men, on two consecutive days, one of which began with a single bout of SIT (random order). Sprint exercise increased TDEE in every research participant (9169 ± 243 vs. 10,111 ± 260 kJ/day; P < 0.0001); the magnitude of increase was 946 ± 62 kJ/day (∼10%). These data provide support for SIT as a strategy for increasing TDEE, and may have implications for healthy body weight maintenance.