INS and obesity due to melanocortin 4 receptor deficiency: These positive and negative feedback regulations and interaction(s) among cytokines, insulin, hypothalamic peptides, BDNF, and PUFAs and their metabolites highlights the complexity of pathobiology of obesity and type 2 DM and the role of various tissues (hypothalamus, adipose tissue, muscle, liver, and immune system) in their pathobiology.