Spexin alleviates insulin resistance in adipose tissue / 中华内分泌代谢杂志

ABSTRACT

Objective:To explore the role and mechanism of exogenous active peptide spexin in regulating insulin resistance in adipose tissue.Methods:High-fat diet induced obesity model(DIO) mice and diabetic model(db/db) mice were given intraperitoneal injection of spexin(50 μg/kg) for 3 consecutive weeks, while each control group was given an equal volume of saline. After the intervention, the body weight, visceral fat weight and plasma biochemical indexes of the mice in each group were analyzed. Real-time fluorescence quantitative PCR was used to detect mRNA levels of Krüppel-like transcription factor 9(KLF9), peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) and glucose transporter 4(GLUT4); Western blotting was used to detect the protein levels of KLF9, PGC-1α, GLUT4 and p-p38/p38 in adipose tissue.Results:Compared with DIO control mice, spexin-treated DIO mice showed a significant reduction in body weight ( P=0.043), adiposity ( P<0.001), glucose ( P<0.001), insulin ( P=0.008), HOMA-IR ( P<0.001) and elevation in glucose tolerance ( P=0.006) and insulin tolerance levels ( P=0.002). Compared with db/db control mice, spexin-treated db/db mice showed a significant reduction in body weight ( P<0.001), adiposity ( P<0.001), glucose ( P=0.041), insulin ( P=0.009), HOMA-IR ( P=0.007) and elevation in glucose tolerance ( P=0.008) and insulin tolerance levels ( P=0.031). In addition, the gene and protein levels of KLF9, PGC-1α and GLUT4 were significantly increased in the adipose tissue of spexin-treated DIO mice compared with DIO control mice [genes ( P<0.001, P<0.001, P=0.005); proteins ( P=0.047, P=0.022, P=0.001)], while p-p38/p38 protein levels were significantly decreased in the adipose tissue of spexin-treated DIO mice compared with DIO control mice ( P=0.002). Moreover, the gene and protein levels of KLF9, PGC-1α and GLUT4 were significantly increased in the adipose tissue of spexin-treated db/db mice compared with db/db control mice [genes ( P<0.001, P<0.001, and P=0.005); proteins ( P=0.001, P=0.004, and P<0.001)], while p-p38/p38 protein levels were significantly decreased in the adipose tissue of spexin-treated db/db mice compared with db/db control mice ( P=0.001). Conclusion:These results suggested that spexin may play a role in ameliorating adipose tissue insulin resistance in DIO mice and db/db mice through regulating p38MAPK-mediated inflammation and KLF9-PGC-1α-GLUT4 pathway-mediated glucose uptake.