LGR5 and obesity due to melanocortin 4 receptor deficiency: Mechanistic studies have demonstrated that in the mammalian intestine, diet-induced obesity increased the number and function of Lgr5+ ISCs by inducing peroxisome proliferator-activated receptor delta, and the enforced PPAR-delta signaling contributed to tumorigenicity in vivo upon loss of the tumor suppressor Apc 56.