Type VI collagen and its cleavage product, endotrophin, cooperatively regulate the adipogenic and lipolytic capacity of adipocytes

Abstract

Type VI collagen (Col6) is a major component of the adipose tissue extracellular matrix (AT ECM), and its levels are elevated during obesity and diabetes. The present study shows that Col6 fibrils play a central role in regulating adipogenesis and lipolysis, with specific roles for each chain constituting Col6, and endotrophin (ETP), a cleavage product of Col6. The holo-Col6 fibrils are required for mature adipocyte differentiation, while only Col6a3 deficient 3T3-L1 adipocytes showed decreased inflammation and adipocyte lipolysis. Col6a3 deficient mice (Col6a3 KO) showed decreased adipocyte size and mass of AT in vivo, due to defect in adipogenic and lipolytic capacity of adipocytes. The overexpression of ETP in high-fat diet induced obese mice further elevated the levels of inflammation and lipolysis. Thus, holo-Col6 fibrils and ETP govern adipocyte function independently of their role as structural supports, and the latter could be an important target for treating adipocyte dysfunction in obesity.