G.P.218: Role of Collagen VI as a soluble factor in the control of glucose and adipose tissue homeostasis

Abstract

Collagen VI is present in the extracellular matrix (ECM) of connective tissues and is enriched in skeletal muscle and adipose tissue, two of the main tissues regulating glycemia. Collagen VI expression is regulated by glucose and lipids and disruption of COL6A1 in mice is associated with improvements in glucose tolerance in the high-fat diet and ob/ob background. Our objective was to elucidate collagen VI ability to regulate glucose and insulin metabolism and investigate if collagen VI defects were associated with metabolic disturbances. The effect of purified collagen VI, I and V, either soluble or as a surface coating, on basal or insulin-stimulated glucose uptake was assessed in myogenic LHCN-M2, C2C12 and L6 cells and preadipocyte SGBS cells. The Insulin-Akt-GS3K signaling pathway was investigated by immunoblot and the expression of genes involved in insulin signaling and glucose transport was analysed by qRT-PCR. Plasma glucose and insulin levels were assessed after a 75 g oral glucose tolerance test in patients. Plasma leptin and adiponectin concentrations were measured by ELISA. Soluble collagen VI significantly induces glucose uptake by muscle cells and adipocytes in a dose and time dependent manner. In contrast, immobilized collagen VI and soluble collagens I and V had no effect. Collagen VI treatment does not induce significant phosphorylation of Akt, GS3K or AS160 in human myotubes but appears to have an effect in gene expression. In a proportion of patients with collagen VI defects we detected abnormally oral glucose tolerance test results and altered leptin and adiponectin plasma levels. In conclusion, soluble COLVI stimulates glucose uptake in skeletal muscle and adipose cells. Our results suggest that it may exert this effect, at least partly, by regulating expression of relevant genes. Our data indicate a novel role for collagen VI in glucose and lipid metabolism which may contribute to the phenotype of patients with mutations in COL6 genes.