m6A Reader HNRNPC Facilitates Adipogenesis by Regulating Cytoskeletal Remodeling through Enhanced Lcp1 mRNA Stability.

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.

Caspase-1 Deficiency Modulates Adipogenesis through Atg7-Mediated Autophagy: An Inflammatory-Independent Mechanism.

Obesity stands as a significant risk factor for type 2 diabetes, hyperlipidemia, and cardiovascular diseases, intertwining increased inflammation and decreased adipogenesis with metabolic disorders. Studies have highlighted the correlation between Caspase-1 and inflammation in obesity, elucidating its essential role in the biological functions of adipose tissue. However, the impact of Caspase-1 on adipogenesis and the underlying mechanisms remain largely elusive. In our study, we observed a positive correlation between Caspase-1 expression and obesity and its association with adipogenesis. In vivo experiments revealed that, under normal diet conditions, Caspase-1 deficiency improved glucose homeostasis, stimulated subcutaneous adipose tissue expansion, and enhanced adipogenesis. Furthermore, our findings indicate that Caspase-1 deficiency promotes the expression of autophagy-related proteins and inhibits autophagy with 3-MA or CQ blocked Caspase-1 deficiency-induced adipogenesis in vitro. Notably, Caspase-1 deficiency promotes adipogenesis via Atg7-mediated autophagy activation. In addition, Caspase-1 deficiency resisted against high-fat diet-induced obesity and glucose intolerance. Our study proposes the downregulation of Caspase-1 as a promising strategy for mitigating obesity and its associated metabolic disorders.

Chemerin as an Inducer of ß Cell Proliferation Mediates Mitochondrial Homeostasis and Promotes ß Cell Mass Expansion.

Loss of the ß cell population is a crucial feature of type 2 diabetes. Restoring the ß cell mass by stimulating ß cell proliferation and preventing its apoptosis was proposed as a therapeutic approach to treating diabetes. Therefore, researchers have been increasingly interested in identifying exogenous factors that can stimulate ß cell proliferation in situ and in vitro. Adipokine chemerin, which is secreted from adipose tissue and the liver, has been identified as a chemokine that plays a critical role in the regulation of metabolism. In this study, we demonstrate that chemerin as a circulating adipokine promotes ß cell proliferation in vivo and in vitro. Chemerin serum levels and the expression of the main receptors within islets are highly regulated under a variety of challenging conditions, including obesity and type 2 diabetes. As compared to their littermates, mice overexpressing chemerin had a larger islet area and increased ß cell mass with both a normal and high-fat diet. Moreover, in chemerin-overexpressed mice, we observed improved mitochondrial homeostasis and increased insulin synthesis. In summary, our findings confirm the potential role of chemerin as an inducer of ß cell proliferation, and they provide novel insights into the helpful strategy to expand ß cell population.