Abstract
Epigenetic signals and chromatin-modifying proteins play critical roles in adipogenesis, which determines the risk of obesity and which has recently attracted increasing interest. Histone demethylase 2A (KDM2A) is an important component of histone demethylase; however, its direct effect on fat deposition remains unclear. Here, a KDM2A loss of function was performed using two unbiased methods, small interfering RNA (siRNA) and Cre-Loxp recombinase systems, to reveal its function in adipogenesis. The results show that the knockdown of KDM2A by siRNAs inhibited the proliferation capacity of 3T3-L1 preadipocytes. Furthermore, the promotion of preadipocyte differentiation was observed in siRNA-treated cells, manifested by the increasing content of lipid droplets and the expression level of adipogenic-related genes. Consistently, the genetic deletion of KDM2A by Adipoq-Cre in primary adipocytes exhibited similar phenotypes to those of 3T3-L1 preadipocytes. Interestingly, the knockdown of KDM2A upregulates the expression level of Transportin 1(TNPO1), which in turn may induce the nuclear translocation of PPARγ and the accumulation of lipid droplets. In conclusion, the ablation of KDM2A inhibits preadipocyte proliferation and promotes its adipogenic differentiation. This work provides direct evidence of the exact role of KDM2A in fat deposition and provides theoretical support for obesity therapy that targets KDM2A.
Highlights
The results indicate that the KDM2A loss of function inhibited preadipocyte proliferation, as assessed by cell counting kit-8 (CCK-8) assay, Ki67 and Edu staining, and promoted the preadipocyte differentiation indicated by an increase in lipid accumulation and an elevation of the expression of adipogenicrelated genes
We report that KDM2A is a negative regulator of adipocyte differentiation; both the knockdown and knockout of KDM2A suppresses the proliferation and promotes the differentiation of adipocytes
The knockdown of KDM2A upregulates the transcription of peroxisome proliferator-activated receptor γ (PPARγ) and promotes its nuclear translocation by Transportin 1 (TNPO1), and subsequently facilitates adipocyte differentiation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Obesity has gradually developed into a global epidemic, and, according to the World. Health Organization (WHO), its prevalence has tripled over the last 40 years [1]. This has resulted in the risk and incidence probability of obesity-related metabolic diseases increasing sharply, including type 2 diabetes (T2D), metabolic syndrome, cardiovascular disease and cancer [2]. The rising cost of living due to the prevalence of obesity and the cost of its prevention makes it necessary to find and develop more effective strategies to prevent and treat obesity [3]
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