# Effects of resistance training on alleviating hypoxia‐induced muscle atrophy: Focus on acetylation of FoxO1

## TL;DR

Resistance training helps prevent muscle atrophy caused by low oxygen levels by affecting FoxO1 acetylation and autophagy.

## Contribution

This study reveals a novel mechanism by which resistance training counteracts hypoxia-induced muscle atrophy through FoxO1 acetylation.

## Key findings

- Resistance training reversed hypoxia-induced decreases in lean body mass and muscle fiber size.
- Hypoxia-induced autophagy was suppressed by resistance training, linked to reduced nuclear FoxO1 and cytoplasmic Ac-FoxO1.
- FoxO1 deacetylation under hypoxia inhibited autophagic proteins and increased myotube diameter in L6 cells.

## Abstract

This study aims to explore the role of FoxO1 and its acetylation in the alleviation of hypoxia‐induced muscle atrophy by resistance training. Forty male Sprague–Dawley rats were randomly divided into four groups: normoxic control group (C), normoxic resistance training group (R), hypoxic control group (H) and hypoxic resistance training group (HR). Rats in R and HR groups were trained on an incremental weight‐bearing ladder every other day, while those in H and HR groups were kept in an environment containing 12.4% O2. After 4 weeks, muscles were collected for analysis. Differentiated L6 myoblasts were analysed in vitro after hypoxia exposure and plasmids transfection (alteration in FoxO1 acetylation). The lean body mass loss, wet weight and fibre cross‐sectional area of extensor digitorum longus of rats were decreased after 4 weeks hypoxia, and the adverse reactions above was reversed by resistance training. At the same time, the increase in hypoxia‐induced autophagy was suppressed, which was accompanied by a decrease in the expression of nuclear FoxO1 and cytoplasmic Ac‐FoxO1 by resistance training. The L6 myotube diameter increased and the expression of autophagic proteins were inhibited under hypoxia via intervening by FoxO1 deacetylation. Overall, resistance training alleviates hypoxia‐induced muscle atrophy by inhibiting nuclear FoxO1 and cytoplasmic Ac‐FoxO1‐mediated autophagy.