NOS2 and obesity due to melanocortin 4 receptor deficiency: However, iNOS upregulation has been touted as both beneficial and detrimental, with the overproduction of NO via iNOS implicated in disease states such as sepsis [4,12], neurodegenerative disease and stroke [62,63], diabetes and obesity-induced insulin resistance [64], pain syndromes [4], and cancer [4].