Abstract
Reduced adipogenesis is a prominent characteristic of aging adipose tissue and is closely tied to the development of metabolic disorders associated with aging. Epigenetic modification plays a crucial role in the aging process, yet the role of N6-methyladenosine (m6A), the most prevalent RNA modification, in regulating adipose tissue aging remains uncertain. Our study found that levels of m6A and its recognition protein, heterogeneous nuclear ribonucleoprotein C (HNRNPC), decrease in adipose tissue as individuals age. Lower levels of HNRNPC were also linked to reduced adipogenesis during aging. Through loss and gain of function experiments with HNRNPC, we established a positive correlation between HNRNPC and adipogenesis in vitro. Hnrnpc-APKO mice displayed decreased adipogenesis, increased insulin resistance, elevated expression of aging-related and inflammation-related genes, decreased lipogenesis-related genes, and other metabolic disorders compared to their littermates. Additionally, we discovered that HNRNPC facilitated the stability of lymphocyte cytosolic protein 1 (Lcp1) mRNA by binding to the m6A motif of LCP1. Overexpression of LCP1 mitigated the inhibition of adipogenesis caused by decreased HNRNPC through modulation of cytoskeletal remodeling. Finally, our findings demonstrate that anti-aging treatments could enhance HNRNPC levels. In conclusion, HNRNPC is positively associated with reduced adipogenesis during aging, and increacing HNRNPC levels through anti-aging treatments highlights its potential as a therapeutic target for addressing metabolic imbalances in adipose tissue related to aging.