Integrative Transcriptomics and Proteomics Analysis Reveals 's Role in Lipid Metabolism.

Abnormalities in lipid metabolism and endoplasmic reticulum (ER) stress are strongly associated with the development of a multitude of pathological conditions, including nonalcoholic fatty liver disease (NAFLD), diabetes mellitus, and obesity. Previous studies have indicated a potential connection between thyroid hormone responsive ( and lipid metabolism and that ER stress may participate in the synthesis of key regulators of adipogenesis. However, the specific mechanisms remain to be investigated. In this study, we explored the roles of in lipid metabolism by interfering with gene expression in mouse mesenchymal stem cells, comparing the effects on adipogenesis between control and interfered groups, and by combining transcriptomic and proteomic analysis. Our results showed that the number of lipid droplets was significantly reduced after interfering with , and the expression levels of key regulators of adipogenesis, such as , , , and , were significantly downregulated. Both transcriptomic and proteomic results showed that the differential genes (proteins) were enriched in the processes of lipolytic regulation, ER stress, cholesterol metabolism, sphingolipid metabolism, PPAR signaling pathway, and glycerophospholipid metabolism. The ER stress marker gene, , was the most significantly downregulated transcription factor. In addition, RT-qPCR validation indicated that the expression levels of PPAR signaling pathway gene ; key genes of lipid droplet generation including , , and ; and ER stress marker gene were significantly downregulated. These suggest that is involved in regulating ER stress and the PPAR signaling pathway, which is closely related to lipid synthesis and metabolism. Interfering with the expression of may be helpful in ameliorating the occurrence of diseases related to abnormalities in lipid metabolism.