Impact of weight cycling on CTRP3 expression, adipose tissue inflammation and insulin sensitivity in C57BL/6J mice.

Abstract

Impacts of weight cycling on C1q/tumor necrosis factor (TNF)-related protein-3 (CTRP3) expression, adipose tissue inflammation and insulin sensitivity in C57BL/6J mice were evaluated in the current study. A total of 30 male C57Bl/6J mice were divided randomly into three groups; normal control (n=10), high-fat diet (OB, n=10) and weight cycling (WC, n=10), which were fed with high-fat diet in the first and last 8 weeks and regular chow in between. Systemic glucose metabolic status and insulin sensitivity were detected by intraperitoneal glucose tolerance test and hyperinsulinemic-euglycemic clamp, respectively. Blood levels of interleukin (IL)-6 and TNF-α were determined using ELISA. Relative CTRP3, IL-6, TNF-α and glucose transporter (GLUT)4 mRNA expression in adipose tissue was detected using reverse transcription-quantitative polymerase chain reaction assays. Relative CTRP3, phosphatidylinositide 3-kinases (PI3K) and protein kinase B (PKB; Ser473) protein expression were detected by western blot analysis. Area under the curve of glucose and glucose infusion rate of the WC group were significantly increased compared with the OB group (P<0.01). CTRP3 mRNA and protein levels of the WC group were significantly decreased by 20.3 and 23.1%, respectively, compared with the OB group (P<0.01). IL-6 and TNF-α protein plasma levels and gene expression in adipose tissue of the WC group were significantly increased compared with the OB group (P<0.01). Expression and phosphorylation of insulin signaling molecules PI3K and PKB (Ser473), respectively and GLUT4 gene expression in adipose tissue of the WC group were significantly decreased compared with the OB group (P<0.01). In conclusion, weight cycling impaired glucose metabolism and insulin sensitivity by decreasing CTRP3, PI3K, phosphorylated-PKB (Ser473) and GLUT4 expression, and increasing IL-6 and TNF-α levels.