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. HIGHLIGHTSO_LIExtracellular vesicles and HDL particles have a distinct sRNA content C_LIO_LIExtracellular vesicles and HDL particles carry both host and nonhost sRNA cargo C_LIO_LIEstrogen deficiency blunts the c-miR-response induced by acute exercise C_LIO_LIExercise responsive miRs in HT users may regulate the choice of energy substrate C_LI