Meanwhile, smoking and obesity bear a complex relationship with COPD aggravation: the adipose tissue is a critical place where cytokines (TNF-a and IL-6) form; adiponectin declines as obesity aggravates, which would enhance the resistance of insulin, circulate radicals and oxidative stress, and aggravate pulmonary inflammation [48–50]. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.