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.

Exercise effects on γ3-AMPK activity, phosphorylation of Akt2 and AS160, and insulin-stimulated glucose uptake in insulin-resistant rat skeletal muscle.

One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle. Prior research on healthy muscle suggests that enhanced postexercise ISGU depends on elevated γ3-AMPK activity leading to greater phosphorylation of Akt substrate of 160 kDa (pAS160) on an AMPK-phosphomotif (Ser704). Phosphorylation of AS160Ser704, in turn, may favor greater insulin-stimulated pAS160 on an Akt-phosphomotif (Thr642) that regulates ISGU. Accordingly, we tested if exercise-induced increases in γ3-AMPK activity and pAS160 on key regulatory sites accompany improved ISGU at 3 h postexercise (3hPEX) in insulin-resistant muscle. Rats fed a high-fat diet (HFD; 2-wk) that induces insulin resistance either performed acute swim-exercise (2 h) or were sedentary (SED). SED rats fed a low-fat diet (LFD; 2 wk) served as healthy controls. Isolated epitrochlearis muscles from 3hPEX and SED rats were analyzed for ISGU, pAS160, pAkt2 (Akt-isoform that phosphorylates pAS160Thr642), and γ1-AMPK and γ3-AMPK activity. ISGU was lower in HFD-SED muscles versus LFD-SED, but this decrement was eliminated in the HFD-3hPEX group. γ3-AMPK activity, but not γ1-AMPK activity, was elevated in HFD-3hPEX muscles versus both SED controls. Furthermore, insulin-stimulated pAS160Thr642, pAS160Ser704, and pAkt2Ser474 in HFD-3hPEX muscles were elevated above HFD-SED and equal to values in LFD-SED muscles, but insulin-independent pAS160Ser704 was unaltered at 3hPEX. These results demonstrated, for the first time in an insulin-resistant model, that the postexercise increase in ISGU was accompanied by sustained enhancement of γ3-AMPK activation and greater pAkt2Ser474. Our working hypothesis is that these changes along with enhanced insulin-stimulated pAS160 increase ISGU of insulin-resistant muscles to values equaling insulin-sensitive sedentary controls.NEW & NOTEWORTHY Earlier research focusing on signaling events linked to increased insulin sensitivity in muscle has rarely evaluated insulin resistant muscle after exercise. We assessed insulin resistant muscle after an exercise protocol that improved insulin-stimulated glucose uptake. Prior exercise also amplified several signaling steps expected to favor enhanced insulin-stimulated glucose uptake: increased γ3-AMP-activated protein kinase activity, greater insulin-stimulated Akt2 phosphorylation on Ser474, and elevated insulin-stimulated Akt substrate of 160 kDa phosphorylation on Ser588, Thr642, and Ser704.

Acute endurance exercise increases Vegfa mRNA expression in adipose tissue of rats during the early stages of weight gain.

The aim of this study was to determine the effects of acute exercise on key factors regulating angiogenesis in adipose tissue. Adipose tissue Vegf-a messenger RNA expression was upregulated immediately after acute exercise (p < 0.05) in rats consuming a high-fat diet, but was lower after exercise (p < 0.05) in rats consuming a low-fat diet. Our working hypothesis is that acute exercise augments angiogenic signaling under conditions when adipose tissue is expanding, and with repeated exercise sessions these signals can accrue to enhance vascularization.