LGR5 and obesity due to melanocortin 4 receptor deficiency: For example, DeClercq and coworkers demonstrated that high-fat diet-induced obesity increases Lgr5-GFP + cell proliferation and numbers through adiponectin signaling [80], as well as inducing prolonged impacts on the proliferation of ISC, expanded crypt depth, villus height, numbers of gut stem cells, and goblet cells in mice [80].