SMAD2 and obesity due to melanocortin 4 receptor deficiency: First, the overexpression of GDF11 could promote survival, differentiation and development of pancreatic β‐cell through SMAD2/3‐PI3K/AKT/FOXO1 signal pathways27, 62, 77 and the second possibility is that GDF11 blocks activation of macrophages and chronic tissue inflammation that plays a crucial role in the development of obesity‐related insulin resistance.76, 78, 79