A1R activation increases lipogenesis (139, 140), adipogenesis (141) and leptin production (142, 143). Over-expression of A1R in adipose tissue in mice protect from obesity-induced insulin resistance (144). A1R KO mice show increased fat mass and body weight, and impaired glucose tolerance and insulin sensitivity (145, 146). Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.