S1PR1 and obesity due to melanocortin 4 receptor deficiency: In this regard, approved FTY720, which acts on ceramide synthesis and S1P1,3,4,5 as either agonist or antagonist depending on cell types is far from ideal, even though they effectively improve metabolic abnormalities induced by obesity in adipose tissue, skeletal muscles, and pancreatic β-cells with rather limited side effects.