Background: 

The adipose tissue-derived cytokine adiponectin plays a major role in whole-body glucose and lipid metabolism. A family of adiponectin paralogs, designated as C1q/tumor necrosis factor-alpha-related proteins (CTRPs), has recently been discovered. However, no data are available on metabolic effects of these adiponectin paralogs in the heart.

Methods: 

Recombinant mouse CTRP1-10 containing an N-terminal His or MBP-Tag were produced in E. coli and purified by affinity chromatography. H9C2 myoblasts or adult rat cardiomyocytes were stimulated with CTRPs in a time and dose dependent manner. Translocation of Glut-1 and Glut-4 from cytosol to cell surface was examined by Western blotting and confocal fluorescence microscopy. Glucose uptake was analyzed with [3H] 3-0-methyl-D-glucose.

Results: 

In H9C2 cells and cardiomyocytes, CTRP 7 and 9 induced phosphorylation of AMPK on Thr172. Increased translocation of Glut-1 (Western Blotting; confocal microscopy) was detected in H9C2 cells after stimulation with CTRP7 and CTRP9, but not by CTRP1, 2, 3, 6 and 10. However, only CTRP9 induced Glut-1 translocation in cardiomyocytes. The translocation of Glut-4 was induced by CTRP7 and CTRP9 in Glut-4-overexpressing H9C2 cells. Furthermore, CTRP7 and CTRP9 induced glucose uptake in H9C2 cells while only CTRP9 increased glucose uptake in cardiomyocytes. Effects on glucose metabolism were abolished after AMPK inhibition.

Summary and Conclusions: 

The adiponectin paralogs CTRP7 and CTRP9 activate AMPK, leading to increased Glut-translocation and enhanced glucose uptake. Thus, members of the growing CTRP family of proteins may provide a therapeutic target in metabolic diseases such as obesity and diabetes.