INS and obesity due to melanocortin 4 receptor deficiency: In obesity, the storage capacity of subcutaneous adipose tissue, the largest white adipose tissue depot, is limited, and further caloric overload leads to fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lip toxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance.