The efficacy of CL316243 appears also to be reduced in the presence of obesity-associated low-grade inflammation [77, 78], as obese mice with adipose tissue dysfunction and increased proinflammatory cytokines showed impaired β3-AR sensitivity to CL316243, leading to catecholamine resistance and reduced EE [91]. The gene discussed is ADRB3; the disease is obesity due to melanocortin 4 receptor deficiency.