From Gut to Fat: Intestinal Epithelial Exosomes Target PDGFRα + Progenitors to Promote Lipogenesis and Counteract Subcutaneous Adipose Tissue Atrophy in Aging.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Age-related subcutaneous adipose tissue (SAT) atrophy is a hallmark of aging, contributing to metabolic dysfunction and systemic aging. The mechanisms underlying SAT atrophy and potential therapeutic strategies remain poorly understood. Here, we report that small intestinal epithelium-derived exosomes (SI-Exos) mediate gut-adipose communication and play a pivotal role in age-related SAT remodeling. We found that the miRNA cargo of SI-Exos undergoes significant age-related changes. Administration of young SI-Exos to aged mice enhanced lipid droplet formation, reversed SAT atrophy, and reduced inflammation in visceral adipose tissue (VAT). These beneficial effects were mediated by young SI-Exos targeting PDGFRα + progenitor cells, the major adipocyte precursors in SAT. Mechanistically, young SI-Exos were enriched with miR-379-5p, which targeted Usp34, a negative regulator of lipogenesis. Inhibition of Usp34 downregulated the Wnt/β-catenin pathway, promoting lipid droplet formation and differentiation of PDGFRα + progenitor cells. Single-cell RNA sequencing analysis further confirmed that young SI-Exos enhanced lipid transport and synthesis in SAT cell populations. Additionally, NK cells were increased. Our findings reveal a previously unrecognized role of SI-Exos in regulating SAT progenitor cell dynamics through the miR-379-5p/Usp34/Wnt/β-catenin axis, offering a potential thera

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.