Wen-pi-tang-Hab-Wu-ling-san, a Polyherbal Medicine, Attenuates ER Stress in 3T3-L1 Preadipocytes by Promoting the Insulin Signaling Pathway

The endoplasmic reticulum (ER) is an organelle that functions to synthesize, fold, and transport proteins. ER stress is a key link between type 2 diabetes (T2D), obesity, and insulin resistance. In this study, we investigated the effect of WHW on the ER stress response and the insulin signaling pathway in 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were differentiated into adipocytes, and ER stress was then induced by treatment with tunicamycin. ER stress-induced adipocytes were treated with different concentrations of WHW for 24 h. The expression of ER stress-related molecules such as X-box-binding protein-1 (XBP-1), glucose-regulated protein 78 (GRP78), C/EBP-homologous protein 10 (CHOP10), and eukaryotic initiation factor 2 alpha (eIF2 alpha) and signaling molecules such as phosphatidylinositol 3-kinase (PI3K), insulin receptor substrates-1 (IRS-1), and c-Jun N-terminal protein kinase (JNK) were investigated. WHW significantly inhibited the expression of XBP-1, GRP78, CHOP10, and eIF2 alpha in ER stress-induced 3T3-L1 adipocytes. WHW also increased the PI3K expression and the IRS-1 phosphorylation but decreased the phosphorylation of JNK in ER stress-induced 3T3-L1 adipocytes. Our results indicate that WHW inhibits ER stress in adipocytes by suppressing the expression of ER stress-mediated molecules and the insulin signaling pathway, suggesting that WHW may be an attractive therapeutic agent for managing T2D.