Astragalus polysaccharide regulates brown adipogenic differentiation through miR-1258-5p-modulated cut-like homeobox 1 expression

Abstract Astragalus polysaccharide (APS) is the major natural active component of Astragalus membranaceus, which has been recognized as one of the most popular herbal medicines worldwide. Enhancing the formation and function of brown adipose tissue increases energy expenditure and hence may potentially be used against obesity and type 2 diabetes. The aim of the present study was to explore the effect and mechanism of APS on brown adipocyte formation. Mouse C3H10T 1/2 cells were subject to APS, and both proliferation and brown adipogenic differentiation were determined. The results showed that APS exhibits a decreased proliferation ability, which is accompanied by downregulated proliferating cell nuclear antigen, cyclin D1, and cyclin-dependent kinase 4. APS promotes the differentiation of C3H10T 1/2 cells into brown adipocytes and induces the expressions of key brown adipogenic transcriptional factors, including CCAAT/enhancer-binding protein β, uncoupling protein 1, and PR domain-containing 16. Importantly, APS enables insulin sensitization in brown adipocytes, which may proceed through activation of the canonical phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and AMP-activated protein kinase (AMPK). Furthermore, the level of cut-like homeobox 1 (CUX1) is positively related to brown adipogenic differentiation, while APS regulates Cux1 expression through interaction with miR-1258-5p. Notably, the promotional effect of APS on brown adipogenic differentiation was abolished by Cux1 knockout. Collectively, our results suggest that APS enhances the differentiation of C3H10T 1/2 cells into brown adipocytes through regulating Cux1 via miR-1258-5p.