Involvement of the IL-27/p38 MAPK/PGC-1α pathway in sleeve gastrectomy-induced metabolic improvement

Abstract

Abstract Sleeve gastrectomy (SG) effectively improves metabolic disorders in individuals with obesity and type 2 diabetes (T2DM), but its molecular mechanism remains unclear. Interleukin 27 (IL-27) improves obesity, insulin resistance and white adipose tissue browning; however, its role in SG-mediated metabolic improvement is unconfirmed. This study aimed to explore the role of IL-27 in metabolic disorders improved by SG in obese T2DM rats. Obese T2DM rats were established and randomly divided into an SG group and a sham operation (control) group. Body weight, food intake, fasting blood glucose levels and insulin resistance indicators were dynamically monitored. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT‒PCR) and immunohistochemistry were used to measure the levels of IL-27 and adiponectin in rat plasma, as well as the expression levels of related molecules in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT); 3T3-L1 adipocyte experiments were performed to clarify the regulatory relationship between IL-27 and adiponectin. Compared with the control group, SG significantly reduced body weight, food intake, fasting blood glucose, and insulin resistance in obese T2DM rats (all P  < 0.05); it also significantly increased the IL-27 levels in plasma, eWAT, and iWAT, and upregulated the expression of the IL-27 receptor (IL-27Rα) in eWAT, and the expression of p38 mitogen-activated protein kinase (p38 MAPK), peroxisome proliferator-activated receptor α (PPAR-α), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and uncoupling protein 1 (UCP-1) in eWAT, as well as UCP-1 in iWAT (all P  < 0.05). In vivo experiments revealed a significant positive correlation between IL-27 and adiponectin levels ( P  < 0.05); in vitro experiments confirmed that IL-27 directly promoted adiponectin expression, whereas adiponectin did not significantly affect IL-27 expression ( P  > 0.05). SG is associated with elevated IL-27 levels and activation of the eWAT p38 MAPK-PGC-1α pathway in obese T2DM rats, accompanied by improved metabolic parameters, suggesting that IL-27 may play a role in SG-induced metabolic improvement.