The impact and potential mechanisms of long noncoding RNA ENST00000521141.1 on human white adipocyte differentiation

Accumulation of visceral white adipose tissue leads to central obesity and is associated with insulin resistance and increased risk of metabolic disease. lncRNAs have been reported to regulate the growth and development of adipocytes, providing new clues for the prevention and treatment of obesity. In the present study, we identified numerous dysregulated lncRNAs by microarray analysis between human differentiated adipocytes and preadipocytes. In addition, we focused on the lncRNA ENST00000521141.1 (abbreviated as lncRNA521141) confirmed by qRT-PCR to be enriched in differentiated adipocytes. Lentivirus-mediated knockdown of lncRNA521141 significantly suppressed adipogenesis as evidenced by reduced lipid accumulation, triglyceride content, and key adipogenic markers expression, while lentivirus-mediated lncRNA521141 overexpression showed no significant effect. Given that lncRNA521141 did not alter the expression of the neighboring gene PEBP4, fluorescence in situ hybridization was employed to elucidate the cellular localization of lncRNA521141, revealing its predominant distribution in the nucleus. RNA-sequencing and western blot analysis further revealed the potential involvement of the PI3K-Akt and thyroid hormone synthesis pathways in lncRNA521141-mediated adipogenic inhibition. Among the differentially expressed genes, PDGFRA expression was significantly upregulated following lncRNA521141 silencing and was closely associated with adipocyte differentiation. Rescue experiments confirmed that knockdown of PDGFRA expression after lncRNA521141 silencing alleviated the inhibitory effects of the reduced lncRNA521141 expression on adipocyte differentiation. In summary, the present study identified lncRNA521141 as a key regulator of adipogenic differentiation in human preadipocytes and elucidated its potential regulatory mechanism, thereby providing new insights and potential intervention targets for treating obesity and its related diseases.