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

Area of Science:

• Endocrinology
• Molecular Biology
• Exercise Physiology

Background:

• Decreased systemic estrogen levels during menopause negatively impact metabolic health through unclear mechanisms.
• Estrogens and exercise are known to improve metabolic health, potentially via circulating microRNA (c-miR) signaling.
• Extracellular vesicles (EVs) are increasingly recognized for their role in intercellular communication, but their cargo, including microRNAs, can be confounded by co-isolated high-density lipoprotein (HDL) particles.

Purpose of the Study:

• To investigate the distinct small RNA (sRNA) content of EVs and HDL particles.
• To examine the effects of exercise on sRNA profiles in EVs and HDL particles.
• To determine the influence of estrogen-based hormone therapy (HT) on exercise-induced sRNA responses in postmenopausal women.

Main Methods:

• Differential isolation and small RNA sequencing of EVs and HDL particles.
• Analysis of sRNA content, including microRNAs (miRs) and transfer RNA-derived sRNAs (tRFs).
• Comparison of sRNA profiles in response to acute exercise in postmenopausal women with and without HT.

Main Results:

• EVs and HDL particles exhibit distinct sRNA profiles, encompassing both host and nonhost sRNAs.
• Acute exercise increased miR abundance in EVs and tRF abundance in HDL particles.
• Estrogen-based HT enabled the exercise-induced miR response in both EVs and HDL particles in postmenopausal women, an effect absent in non-users.

Conclusions:

• EVs and HDL particles serve as distinct carriers of sRNAs with unique responses to exercise.
• Estrogen plays a critical role in mediating the exercise-induced circulating sRNA response in postmenopausal women.
• Understanding these distinct pathways is crucial for elucidating menopause-related metabolic dysregulation and developing targeted therapies.