GCG and obesity due to melanocortin 4 receptor deficiency: Similarly, GPR40 knock-out animals showed significantly reduced plasma GIP and GLP-1 levels on a high-fat diet, yet GPR40−/− mice are not significantly protected from developing diet induced obesity, and different laboratories have reported inconsistent effects on glucose homeostasis in high-fat fed mice (Edfalk, Steneberg, & Edlund, 2008; Kebede et al., 2008; Lan et al., 2008; Steneberg, Rubins, Bartoov-Shifman, Walker, & Edlund, 2005).