CLOCK and obesity due to melanocortin 4 receptor deficiency: In this paper, we review multiple calcium signaling pathways, including the IP3 (inositol 1,4,5-trisphosphate)-Ca2+ (calcium ion) pathway, the p38-MAPK (mitogen-activated protein kinase) pathway, and the calmodulin binding pathway, which are involved in biological clock, intestinal microbial activity, and nerve excitability to regulate food intake, metabolism, and differentiation of adipocytes in mammals, resulting in the improvement of obesity.