Alternatively, reduced proliferation is suggested by upregulation of Cdkn1a/p21 in Camk2n1−/− EAT, which has been shown elsewhere to prevent obesity and adipocyte hyperplasia,37 and downregulation of Rbl1/p107 and Cdk1 that have been shown by others to be pro-obesogenic and upregulated in obesity.38 Furthermore, upregulation of Id3 and downregulation of C1s and C4 provide additional mechanisms for reduced adiponectin production,39 reduced adiposity, and increased insulin sensitivity.32,40. This evidence concerns the gene C1S and obesity due to melanocortin 4 receptor deficiency.