Lipotoxicity results from increased serum free fatty acids (FFA) levels and ectopic lipid deposits, which occurs when the storage capacity of adipocytes is overwhelmed (e.g., during obesity) or impaired (e.g., in lipoatrophic or lipodystrophic diseases), and is subjected to a vicious cycle through loss of insulin’s antilipolytic effect in insulin resistant WAT. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.