Implication of satellite cell behaviors in capillary growth via VEGF expression-independent mechanism in response to mechanical loading in HeyL-null mice

Angiogenesis and muscle satellite cell (SC)-mediated myonuclear accretion are considered essential for the robust response of contraction-induced muscle hypertrophy. Moreover, both myonucleus and SCs are physically adjacent to capillaries and are the major sites for the expression of proangiogenic factors, such as VEGF, in the skeletal muscle. Thus, events involving the addition of new myonuclei via activation of SCs may play an important role in angiogenesis during muscle hypertrophy. However, the relevance among myonuclei number, capillary density, and angiogenesis factor is not demonstrated. The Notch effector HeyL is specifically expressed in SCs in skeletal muscle and is crucial for SC proliferation by inhibiting MyoD in overload-induced muscle hypertrophy. Here, we tested whether the addition of new myonuclei by SC in overloaded muscle is associated with angiogenic adaptation by reanalyzing skeletal muscle from HeyL knockout (KO) mice, which show blunted responses of SC proliferation, myonucleus addition, and overload-induced muscle hypertrophy. Reanalysis confirmed blunted SC proliferation and myonuclear accretion in the plantaris muscle of HeyL-KO mice 9 weeks after synergist ablation. Interestingly, the increase in capillary-fiber ratio observed in WT mice was impaired in HeyL-KO mice. In both WT and HeyL-KO mice, the expression of VEGFA and VEGFB was similarly increased in response to overload. In addition, the expression pattern of TSP-1, a negative regulator of angiogenesis, was also not changed between WT and HeyL-KO mice. Collectively, these results suggest that SCs activation-myonuclear accretion plays a crucial role in angiogenesis during overload-induced muscle hypertrophy via independent of angiogenesis regulators.

Muscle hypertrophy and strength gains after resistance training with different volume matched loads: a systematic review and meta-analysis.

The purpose of this paper was to conduct a systematic review and meta-analysis of studies that compared muscle hypertrophy and strength gains between resistance training protocols employing very low (VLL<30% of 1RM or >35 RM), low (LL30%-59% of 1RM, or 16–35 RM), moderate (ML60%-79% of 1RM, or 8 -15RM) and high load (HL≥80% of 1RM, or ≤7 RM) with matched volume loads (sets x reps x weight). A pooled analysis of the standardized mean difference for 1RM strength outcomes across the studies showed a benefit favoring HL vs. LL and vs. ML; and favoring ML vs. LL. Results from LL and VLL indicated little difference. A pooled analysis of the standardized mean difference for hypertrophy outcomes across all studies showed no differences between the training loads. Our findings indicate that, when volume load is equated between conditions, the highest loads induce superior dynamic strength gains. Alternatively, hypertrophic adaptations are similar irrespective of the magnitude of load. NOVELTY BULLETS: • Training with higher loads elicits greater gains in 1RM muscle strength when compared to lower loads, even when volume load is equated between conditions. • Muscle hypertrophy is similar irrespective of the magnitude of load, even when volume load is equated between conditions.

Effects of Acute and Chronic Resistance Exercise on the Skeletal Muscle Metabolome

Resistance training promotes metabolic health and stimulates muscle hypertrophy, but the precise routes by which resistance exercise (RE) conveys these health benefits is largely unknown. Aim: To investigate how acute RE affects human skeletal muscle metabolism. Methods: We collected vastus lateralis biopsies from six healthy male untrained volunteers at rest, before the first of 13 RE training sessions, and 45 min after the first and last bouts of RE. Biopsies were analysed using untargeted mass spectrometry-based metabolomics. Results: We measured 617 metabolites covering a broad range of metabolic pathways. In the untrained state RE altered 33 metabolites, including increased 3-methylhistidine and 1-carboxylethylvaline, suggesting increased protein breakdown, as well as metabolites linked to ATP (xanthosine) and NAD (N1-methyl-2-pyridone-5-carboxamide) metabolism; the bile acid chenodeoxycholate also increased in response to RE in muscle opposing previous findings in blood. Resistance training led to muscle hypertrophy, with slow type I and fast/intermediate type II muscle fibre diameter increasing by 10.7% and 10.4%, respectively. Comparison of post-exercise metabolite levels between trained and untrained state revealed alterations of 46 metabolites, including decreased N-acetylated ketogenic amino acids and increased beta-citrylglutamate which might support growth. Only five of the metabolites that changed after acute exercise in the untrained state were altered after chronic training, indicating that training induces multiple metabolic changes not directly related to the acute exercise response. Conclusion: The human skeletal muscle metabolome is sensitive towards acute RE in the trained and untrained states and reflects a broad range of adaptive processes in response to repeated stimulation.