Extracellular vesicles and high-density lipoproteins: Exercise and estrogen-responsive small RNA carriers

Abstract

Decreased systemic estrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both estrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signaling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that estrogen deficiency caused by menopause blunts acute exercise-induced systemic miR-response in both EV and HDL particles.

Defining the influence of size‐exclusion chromatography fraction window and ultrafiltration column choice on extracellular vesicle recovery in a skeletal muscle model

“…Additional contamination factors, such as other lipids or metabolites, were not accounted for in our research. Currently, soluble proteins or miRNAs are the most studied contaminants alongside lipoproteins in in vitro (Böing et al., 2014; Coenen‐Stass et al., 2019; Pavani et al., 2020) and in vivo research (Karvinen et al., 2022; Kobayashi et al., 2021; Maggio et al., 2023). Future studies will be needed to better identify the extent of non‐lipoprotein contaminants in EV preparations, particularly for SM applications.…”