[41] In contrast to the increase in gene expression of adiponectin we observed at 5 weeks of age, 20 week-old male FTO-4 mice showed a decrease in plasma adiponectin levels. [9] This reduction in plasma adiponectin levels was also observed in rodents on a high fat diet [42], [43] and in humans with obesity and insulin resistance. [44]–[46] However, the reduction in adiponectin levels might take longer to occur, as the stimulatory effect of caloric restriction on adiponectin gene expression was only detectable after long-term caloric restriction and not after short-term restriction. [47]. This evidence concerns the gene ADIPOQ and obesity due to melanocortin 4 receptor deficiency.