miR‐125a‐3p regulates the expression of FSTL1, a pro‐inflammatory factor, during adipogenic differentiation, and inhibits adipogenesis in mice

Abstract

AbstractAdipogenesis is tightly regulated by various factors, including genes and microRNAs. Excessive fat deposition is the key feature of obesity, which is a low‐grade chronic inflammatory disease. Follistatin‐like 1 (FSTL1) has been reported to be an important mediator involved in various inflammatory diseases. However, the underlying mechanism of FSTL1 in preadipocyte differentiation and inflammatory response is still unclear. The current study was designed to explore the biological function and potential mechanism of FSTL1 in mouse subcutaneous preadipocyte differentiation. We found that FSTL1 was highly expressed in the early stage of differentiation and subsequently decreased sharply, suggesting that FSTL1 played a possible role in adipogenesis. Meanwhile, the gain‐ and loss‐of‐function assays showed that FSTL1 was not only involved in the inflammatory response by inducing the expression of pro‐inflammatory factors IL‐1β and CCL2 but also significantly attenuated preadipocyte differentiation, as evidenced by the reduction of lipid accumulation and the levels of adipogenic genes, including PPARγ and FABP4. In addition, the target gene prediction and luciferase reporter assay validated that miR‐125a‐3p targeted the 3′ UTR region of FSTL1. These results demonstrated that miR‐125a‐3p negatively regulated the expression of FSTL1 at the mRNA and protein levels. Furthermore, overexpressing miR‐125a‐3p in preadipocytes dramatically accelerated adipogenic differentiation and downregulated the levels of IL‐1β and CCL2, which were in accordance with the knockdown of FSTL1. On the contrary, treatment with miR‐125a‐3p inhibitors attenuated adipogenesis but induced the expression of inflammatory genes. In summary, this study suggests a positive function of FSTL1 in adipocyte‐induced inflammation and negatively regulates preadipocyte differentiation. Further studies demonstrated that miR‐125a‐3p could reverse the effect by targeting FSTL1, which might provide a better understanding of treating obesity‐related inflammatory diseases.