Acylethanolamides (FAEs) are lipid transmitters released upon demand from membrane phospholipids. The main transmitters of this family are anandamide, oleoylethanolamide and palmithylethanolamide. They act in a variety of receptors including cannabinoid receptors, peroxisome proliferators-activated receptor alpha, vanilloid receptors and several orphan receptors like GPR119 anf GPR55. Anandamide acting in CB1 receptors promotes overfeeding. Its administration increases fatty acid biosynthesis in the liver and lipogenesis in the adipose tissue. Anandamide acting in CB1 receptors in the endocrine pancreas increases glucose-dependent insuline and glucagon release, favouring the availability of glucose to be incorporated into the adipose tissue. Blockade of anandamide effects with the cannabinoid CB1 receptor antagonist Rimonabant results in weight loss and improvement in metabolic parameters (dyslipemia and diabetes) in humans suffering complicated obesity. Oleoylethanolamide has the opposite profile of anandamide: it induces satiety, increases lypolysis, blocks glucose incorporation into the adipose tissue and lowers cholesterol and triglycerides. Combined administration of oleoylethanolamide and Rimonabant to obese animals improved the separate actions on feeding and metabolism obtained with the tratment of each compound when administered alone. New targets of anandamide and oleoylethanolamide includes enzymes modulating lipid biosynthesis such as stearoyl coenzymeA desaturase 1 (SCD1) a key microsomal enzyme involved in obese phenotypes.

Overall, FAEs emerge as a crucial system in the regulation of energy homeostasis, providing new frameworks for the development of therapies against obesity. Supported by MEC SAF 04-07762, ISCIII RD06/001, Proyectos de Excelencia de la Consejeria de Salud, Junta de Andalucia.