Previously, we demonstrated that various hypoxia-induced matrix metalloproteinases (MMPs) are directly involved in the cleavage of COL6A3 to generate endotrophin in obese adipose tissue; thus, inhibition of endotrophin generation by blocking MMP access could be beneficial for treating obesity-related metabolic disease. This evidence concerns the gene COL6A3 and obesity due to melanocortin 4 receptor deficiency.