Moreover, because plasma leptin has been shown to positively associate with the number of activated microglia in the hypothalamus of mice fed with a high fat diet, it is possible that in obesity, insulin resistance can lead to not only dysregulated peripheral immune responses, but also maladaptive neuroinflammatory states that ultimately contribute to energy imbalance and diet-induced obesity [177]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.