N4BP2L1 interacts with dynactin and contributes to GLUT4 trafficking and glucose uptake in adipocytes.

It was reported previously that N4bp2l1 expression increases in 3T3-L1 cells in a differentiation-dependent manner and N4bp2l1 knockdown suppresses adipocyte differentiation. However, the physiological function of N4BP2L1 in adipocytes remains unknown. This study aimed to elucidate the physiological mechanism of N4bp2l1 expression and the role of N4BP2L1 in the physiological function of adipocytes. Analysis of gene expression levels of N4bp2l1 in adipose tissue during feeding in mice was conducted. Identification of transcription factors that regulate N4bp2l1 expression was conducted using a reporter assay. Investigation of N4BP2L1-interacting proteins was carried out using immunoprecipitation. A GLUT4 translocation assay and a glucose uptake assay in 3T3-L1 adipocytes were performed using N4bp2l1 overexpression and knockdown adenovirus. The results indicated that N4bp2l1 is a novel FoxO1 target gene and its expression is controlled by the insulin-mediated regulation of FoxO1. N4BP2L1 interacts with dynactin, which binds to the microtubule motor dynein, indicating that N4BP2L1 is involved in GLUT4 trafficking and glucose uptake in 3T3-L1 adipocytes. Our results suggest that N4BP2L1 is involved in adipocyte homeostasis by interacting with dynein-dynactin and affecting GLUT4-mediated glucose uptake and the insulin signaling pathway.