ADIPOQ and obesity due to melanocortin 4 receptor deficiency: Within this view, once peripheral IR is established in obesity, the increasing influx of free fatty acids and inflammatory cytokines, and adipokines (i.e., adiponectin) from the impaired adipose tissue to the liver results in a state of oxidative stress and inflammation due to the activation of Kupfer cells, mitochondria damage, endoplasmic reticulum (ER) stress, and increased production of reactive oxygen species (ROS) [9,13,14].