Although, switching to a LFD is effective in weight-reduction and improves metabolic health parameters in obesity [18], weight-reduction with LFD in the TLR5−/− mice resulted in a different response regarding the change of weight of epididymal WAT, glucose tolerance, and cytokines response in the serum and adipose tissue compared to the C57BL/6 mice. This evidence concerns the gene TLR5 and obesity due to melanocortin 4 receptor deficiency.