LEP and obesity due to melanocortin 4 receptor deficiency: While obesity in fa/fa Zucker rats is caused by a mutation of the leptin receptor, rimonabant acts to increase leptin uptake by the kidney, which has been shown to reduce proximal tubule metabolic activity.52 Therefore, improvement in renal function in these rats may have occurred due to mechanisms related to leptin's role in proximal tubule cell metabolism,52–54 as opposed to a direct action on the EC system.