Biology subjects

Eftestoel, E.

Publications and source records attributed to Eftestoel, E..

3 recordsLinked to original sources

bioRxiv2021

A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats

One of the ideas stemming from the discovery of a cellular memory in muscle cells has been that an early exercise period could induce a long-term muscle memory, boosting the effects of exercise later in life. In general muscles are more plastic in younger animals, so we devised a 5-week climbing exercise scheme with food reward administered to juvenile rats (post-natal week 4-9). The juvenile exercise increased fiber cross-sectional area (fCSA), and boosted nuclear accretion. Subsequently the animals were subjected to 10 weeks of detraining (week 9-19, standard caging). During this period fCSA became similar in the animals that had been climbing compared to Naive controls, but the elevated number of myonuclei induced by the climbing were maintained. When the Naive rats were subjected to two weeks of adult exercise (week 19-21) there was little effect on fCSA, while the previously trained rats displayed an increase of 19%. Similarly, when the rats were subjected to unilateral surgical overload in lieu of the adult climbing exercise, the increase in fCSA was 20% (juvenile climbing group) and 11% (Naive rats) compared to the contralateral leg. This demonstrated that juvenile exercise can establish a muscle memory. The juvenile climbing exercise with food reward led to leaner animals with lower body weight. These differences were to some extent maintained throughout the adult detraining period in spite of all animals being fed ad libitum, indicating a form of body weight memory.

physiology↗

bioRxiv2021

The epigenetic landscape in purified myonuclei from fast and slow muscles

Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost completely fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where less than 60% of the nuclei are inside muscle fibers. Since cellular homogeneity is critical in epigenome-wide association studies we devised a new method for purifying skeletal muscle nuclei from whole tissue based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labeling and a magnetic-assisted sorting approach we were able to sort out myonuclei with 95% purity. The sorting eliminated influence from other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the functional properties of the two muscles each with a distinct regulatory program involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles are also regulated by different sets of transcription factors; e.g. in soleus binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SOX1 binding sites were found to be overrepresented. In addition, novel factors for muscle regulation such as MAF, ZFX and ZBTB14 were identified.

physiology↗

bioRxiv2021

JNK activation in TA and EDL muscle is load-dependent in rats receiving identical excitation patterns

ABSTACTO_ST_ABSAimC_ST_ABSAs the excitation-contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input is poorly understood. Herein, we use a rat in-vivo strength training setup with an electrically induced standardized excitation pattern previously shown to lead to a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load per se on molecular signalling. MethodsAnaesthetized rats were subjected to unliteral identical electrically-paced contractions of the TA and EDL muscles under a high or low load for a duration of 2, 10 or 28-minutes. Muscle soluble proteins were extracted, and abundance and specific phosphorylations of FAK, mTOR, p70S6K and JNK were measured. Effects of exercise, load, muscle and exercise duration were assessed. ResultsSpecific phosphorylation of S2448-mTOR, T421/S424-p70S6K and T183/Y185-JNK was increased after 28-minutes of exercise under the high- and low-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 minutes of exercise, respectively, but greatest after 28-minutes of exercise. T183/Y185-JNK and S2448-mTOR demonstrated a load-dependent increase in phosphorylation in the exercised muscles that for mTOR depended on muscle type. The abundance of all four kinases was higher in TA compared to EDL muscle. FAK and JNK abundance was reduced after 28 minutes of exercise in both the exercised and control muscle. ConclusionThe current study shows that JNK and mTOR activation is load-driven, and together with muscle-type specific mTOR and p70S6K effects it may drive muscle-type specific exercise and load-responses.

physiology↗