Author(s): YANG, Z., QIANGMAN, W., YAN, C., XINYAN, W., Institution: CHINA INSTITUTION OF SPORT SCIENCE, Country: CHINA, Abstract-ID: 2065

INTRODUCTION:
Insulin resistance (IR) significantly contributes to metabolic associated fatty liver disease (MAFLD). Pole walking, a specific form of exercise, not only reduces IR-associated risk factors but also decreases visceral fat, which ameliorates IR. Emerging findings reveal that long-term exercise-derived circulating exosomes protect against IR or metabolic syndrome (MS) via exosomal miRNAs[1]. However, mechanisms underlying these effects, particularly through exosomal changes, are not fully understood.
METHODS:
Visceral fat levels were assessed in MAFLD patients utilizing magnetic resonance imaging of proton density fat fraction(MRI-PDFF), comparing individuals enrolled in a 12-week pole walking program with a non-exercising control group. Additionally, plasma exosomes were isolated from both cohorts to investigate the potential impact of pole walking exercise on exosomal profiles.A novel miRNA, miR-1197, was identified using a miRNA microarray. Its expression was analyzed in db/db mice and high-fat diet (HFD) mice livers via quantitative real-time PCR (qRT-PCR). To validate the biological function of miR-1197, we performed loss-of-function and gain-of-function experiments, and the underlying mechanism of miR-1197 in the prevention and treatment of MAFLD was examined with RT-PCR and Western Blot.
RESULTS:
MRI-PDFF showed that liver fat levels in the exercise group were significantly reduced. qRT-PCR analysis indicated that miR-1197 was significantly decreased in obese mice, and overexpression of miR-1197 could improve IR; whereas the knockdown of miR-1197 produced the opposite results. Moreover, we determined that miR-1197 could bind to PTEN. In addition, we observed a significant upregulation of miR-1197 expression in the plasma exosomes of athletes. Eventually, we indicated that miR-1197 could play a key role in pole walking-mediated insulin sensitivity through regulating PTEN.
CONCLUSION:
Our study highlights exosomal miRNA, exo-miR-1197, as a potential regulator of insulin signaling through PTEN modulation. This miRNA may offer a promising therapeutic target for the development of MAFLD.
1. Hou Z, Qin X, Hu Y, Zhang X, Li G, Wu J, Li J, Sha J, Chen J, Xia J, Wang L, Gao F. Longterm Exercise-Derived Exosomal miR-342-5p: A Novel Exerkine for Cardioprotection. Circ Res. 2019 Apr 26;124(9):1386-1400. doi: 10.1161/CIRCRESAHA.118.314635. PMID: 30879399.