The direct involvement of tumor-derived factors in promoting anorexia has been proposed.141, 142 Coherently, the bioactive lipid sphingosine-1-phosphate, which is involved in cancer progression and is produced by several tumors,143 has been recently shown to promote energy expenditure and anorexia.135 Increased engagement of sphingosine-1-phosphate-receptor on hypothalamic neurons promotes increased temperature and oxygen consumption, while decreasing food intake.135. This evidence concerns the gene S1PR1 and Anorexia.