Finally, although our strategy to identify transcriptional regulators of COL6A3 coupled with overexpression assays revealed PRRX1 as a potent regulator of COL6A3 in vitro, and these factors showed strong joint correlations with obesity and insulin resistance, the physiological relevance of this relationship remains to be demonstrated in vivo. Here, PRRX1 is linked to obesity due to melanocortin 4 receptor deficiency.