In addition to a maladaptive role for ChREBP in promoting excessive glucose production, three out of four liver-selective ChREBP loss-of-function studies show that hepatic ChREBP is essential for the development of obesity, hyperinsulinemia, and systemic insulin resistance (Fig. 3A) (79, 80, 81, 82). This evidence concerns the gene MLXIPL and obesity due to melanocortin 4 receptor deficiency.