FNDC5 and obesity due to melanocortin 4 receptor deficiency: Alternatively, or concurrently, the reduced irisin levels might be attributed to impairment of FNDC5 cleavage into irisin in the context of obesity [82] or to mechanisms directly related to elevated proinflammatory cytokines as previously proposed in pediatric subjects with type 2 diabetes mellitus (T2DM) [83].