Reduced Expression of Collagen VI Alpha 3 (COL6A3) Confers Resistance to Inflammation-Induced MCP1 Expression in Adipocytes

Obesity, 2016, Gesta et al

Reduction of COL6A3, a novel target discovered by Berg’s Interrogative Biology platform, protects against inflammation associated with obesity

Authors: Gesta S, Guntur K, Majumdar ID, Akella S, Vishnudas VK, Sarangarajan R, Narain NR

Inflammation of fat tissue has been associated with systemic metabolic abnormalities in patients with obesity. In fat tissue, collagen VI, which consists of three major types, COL6A1, COL6A2 and COL6A3, is a major component of the extracellular matrix and an important modulator of systemic metabolism. Collagen type VI alpha 3 (COL6A3) expression in fat tissue has been reported to be associated with obesity, inflammation, and insulin resistance in humans and rodents. Col6a3 was identified by the Berg Interrogative Biology™ discovery platform as a key node in the disease-normal differential human obesity model. Herein, we report a causal link between COL6A3 and inflammation in human fat cells. By engineering human fat cells to have low levels of Col6a3, we found that expression and release of a specific inflammatory molecule, called monocyte chemoattractant protein 1 (MCP1), was markedly reduced. In addition, human fat cells with low levels of Col6a3 were less sensitive to inflammatory cues, exhibiting a “protection” against inflammation. Finally, treatment of human fat cells with an enzyme that degrades collagen VI elicited identical protection against inflammation, highlighting a therapeutic potential for reduction of COL6A3 expression in fat cells for treatment of obesity induced inflammation and associated metabolic disorders.