Impact of Aging and High-Fat Diet on Adipose Tissue-Derived Extracellular Vesicle miRNA Profiles in Mice

Background: Middle-aged adults show the highest obesity rates, leading to significant health complications in later years. Obesity triggers the release of altered molecules including extracellular vesicles (EVs) from excess adipose tissue (AT), contributing to various health complications. In this study, we assessed the effects of age and high-fat diet (HFD) on white AT-derived EV miRNA profiles to understand their potential roles in aging and obesity. Hypothesis: Our hypothesis is that the white AT-derived EV miRNA profiles of middle-aged mice fed HFD will demonstrate deleterious features due to the potential synergistic effects of aging and long-term HFD consumption. Method: C57BL/6 male mice were subjected to a normal chow diet (NCD) or a HFD for either 10-12 weeks (young mice, n=10) or 50-61 weeks (middle-aged mice, n=12). After evaluating metabolic characteristics, white AT-derived EV miRNAs were profiled using a NanoString miRNA panel (n=599). Results: Middle-aged mice exhibited obesity regardless of diet. Young mice fed HFD showed similar metabolic traits to middle-aged mice. In NCD group, 131 differentially expressed miRNAs (DE-miRNAs) emerged in middle-aged mice compared to young mice, including miR-21, miR-148a, and miR-29a associated with cancer, neuro/psychological disorders and reproductive diseases. In HFD group, 55 DE-miRNAs were revealed in middle-aged mice compared to young mice. These miRNAs were associated with significantly suppressed IGF1R activity. Conclusion: This study has demonstrated the altered characteristics of WAT EV miRNAs by aging and diet. Aging and diet induce significant changes in EV miRNA profiles of AT. We suggest that there might be a selective sorting mechanism of miRNAs in AT EVs, contributing to the disease progress or pathogenesis related to aging and obesity. We also suggest that AT EVs in middle-aged mice fed HFD might play a protective role in aging and obesity by inhibiting IGF1R activity. University of Iowa College of Nursing. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.