Understanding the appetite modulation pathways: The role of the FFA1 and FFA4 receptors

Pharmaconutrition is an area of current interest, especially concerning the advances in the pharmacology of nutrient-sensing receptors, as have been accomplished in the last 20 years. The family of free fatty acid (FFA) receptors is composed of four members, sequentially named as FFA1 to FFA4, which are activated by the short to long-chain fatty acids. The affinity of the FFA1 and FFA4 receptors for the omega-3 polyunsaturated fatty acids prompted pre-clinical and clinical investigations regarding their involvement in metabolic diseases. The main studies have been focused on the receptors' expression analyses, the featuring of knockout mice, and the assessment of selective synthetic ligands. These clearly have indicated a relevant role for FFA1 and FFA4 in the peripheral and central circuits for the regulation of energetic metabolism. This review article aimed to discuss the relevance of the FFA1 and FFA4 receptors in appetite-related complications, mainly related to obesity, cancer cachexia, and anorexia in the elderly, emphasizing whether their pharmacological modulation might be useful for the management of these disorders.