Obesity Reprogrammes Adipose Extracellular Vesicles to Induce Muscle Atrophy via miR-150-5p-Mediated Transcriptional...

Area of Science:

• Cell Biology
• Metabolic Health
• Aging Research

Background:

• Sarcopenic obesity, characterized by excess fat and reduced muscle mass, is a growing concern in aging populations, leading to poor physical and metabolic health.
• Adipose tissue-secreted factors are implicated in muscle decline, but the precise mechanisms, particularly involving extracellular vesicles (EVs) and their microRNA (miRNA) cargo, are not fully understood.

Purpose of the Study:

• To investigate the role of extracellular vesicles (EVs) derived from adipose tissue of lean versus non-lean donors in mediating communication with muscle cells.
• To determine if EVs from non-lean donors induce muscle atrophy and identify specific molecular mechanisms, including miRNA involvement, in an age-dependent manner.

Main Methods:

• Isolation and characterization of EVs from adipose-conditioned media of lean and non-lean human donors across different age groups.
• Treatment of primary human myotubes with lean or non-lean EVs to assess effects on myotube thickness and gene expression via bulk RNA sequencing.
• Profiling of EV miRNA cargo using small RNA-seq and validation of specific miRNAs, including miR-150-5p, with qPCR and functional inhibition studies.

Main Results:

• EVs from non-lean donors significantly reduced myotube thickness in older adult-derived myotubes, but not in younger ones, indicating an age-dependent, BMI-specific effect.
• Non-lean EVs increased MAFbx expression and induced transcriptomic changes in myotubes, enriched in inflammatory and oxidative stress pathways.
• miR-150-5p and miR-193b-5p were upregulated in non-lean EVs; inhibiting miR-150-5p partially rescued myotube thickness and reduced MAFbx expression.

Conclusions:

• Extracellular vesicles from non-lean adipose tissue promote muscle atrophy and alter gene expression in an age-dependent manner.
• The findings highlight a mechanistic role for EV-derived miR-150-5p in adipose-muscle signaling, contributing to muscle loss in sarcopenic obesity.
• Targeting EV-derived miRNAs presents a potential therapeutic strategy to counteract muscle wasting associated with obesity and aging.