From a physiological perspective, molecular mechanisms of mitochondrial energy deficits, inflammation with elevated IL6 and TNF, oxidative stress, hypothalamic-pituitary adrenal axis dysfunction, autonomic dysfunction, obesity and adipokine inflammation, and other processes may contribute to fatigue in a wide variety of chronic autoimmune, neoplastic, infectious, cardiac, pulmonary, joint, brain, kidney, and other disease settings (Matura et al., 2018). The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.