Karvinen, S. | bioRxiv Science

bioRxiv2024

Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise

ObjectiveEstrogen deficiency is associated with unfavorable changes in body composition and metabolic health. While physical activity ameliorates several of the negative effects, loss of ovarian function is associated with decreased physical activity levels. It has been proposed that the changes in brain neurochemical levels and /or impaired skeletal muscle function may underlie this phenomenon. MethodsWe studied the effect of estrogen deficiency induced via ovariectomy (OVX) in female Wistar rats (n=64). Rats underwent either sham or OVX surgery and were allocated thereafter into four groups matched for body mass and maximal running capacity: sham/control, sham/max, OVX/control, and OVX/max, of which the max groups had maximal running test before euthanasia to induce acute response to exercise. Metabolism, spontaneous activity, and maximal running capacity were measured before (PRE) and after (POST) the surgeries. Three months following the surgery, rats were euthanized, and blood and tissue samples harvested. Proteins were analyzed from gastrocnemius muscle and retroperitoneal adipose tissue via Western blot. Brain neurochemical markers were measured from nucleus accumbens (NA) and hippocampus (HC) using ultra-high performance liquid chromatography. ResultsOVX had lower basal energy expenditure and higher body mass and retroperitoneal adipose tissue mass compared with sham group (p[≤]0.005). OVX reduced maximal running capacity by 17% (p=0.005) with no changes in muscle mass or phosphorylated form of regulatory light chain (pRLC) in gastrocnemius muscle. OVX was associated with lower serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level in the NA compared with sham (p=0.007). In response to acute exercise, OVX was associated with low serotonin level in the HC and high level in the NA (p[≤]0.024). ConclusionsOur results highlight that OVX reduces maximal running capacity and affects the response of brain neurochemical levels to acute exercise in a brain region-specific manner. These results may offer mechanistic insight into why OVX reduces willingness to exercise.

molecular biology↗

bioRxiv2023

Menopausal transition alters female skeletal muscle transcriptome

Menopause is associated with unfavorable changes in body composition. Skeletal muscle cells are targets of hormonal regulation and are affected by the interplay between coding and non-coding RNAs. Muscle transcriptome, including messenger-RNA (mRNA), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) has not previously been studied in women during the menopausal transition. Thus, we took a multi-RNA omics approach to get insight into transcriptome-wide events of menopause. Our study included baseline and follow-up muscle samples from seven early (EarlyMT) and 17 late perimenopausal (LateMT) women transitioning to early postmenopause during the study. Total RNA was sequenced and differential expression (DE) of the transcriptome was investigated. The potential gene functions were investigated with pathway analyses and protein level expression with Western Blot. We found 30 DE mRNA genes in EarlyMT and 19 in LateMT participating in pathways controlling cell death, growth, and interactions with external environment. Lack of protein level changes may indicate a specific role of the regulatory RNAs during menopause. Ten DE lncRNA transcripts were identified but did not result in DE lncRNAs genes. No DE miRNAs were found. Despite the lack of DE findings in regulatory RNAs, we identified putative regulatory networks, likely to be affected by estradiol availability. The changes in gene expression were correlated with observed changes in body composition variables, indicating muscularity and adiposity regulators to be affected by menopausal transition. In essence, the observed DE genes and their regulatory networks may offer novel mechanistic insights on factors affecting body composition during and after menopause.

molecular biology↗