Fat to treat fat: Emerging relationship between dietary PUFA, endocannabinoids, and obesity

► The endocannabinoid system is comprised of ligands, receptors and synthesis/degradation enzymes. ► Overstimulation of endocannabinoid signaling is highly probable to play a causal role in obesity. ► Evidence linking the types of fatty acids to obesity and the endocannabinoid system is needed. ► Dietary n-3 PUFA were reported to lower the tissue levels of endocannabinoids AEA and 2-AG. ► The n-3 PUFA, EPA and DHA, appear to reverse the obesogenic effects of dietary n-6 PUFA. ► EPA and DHA reduce arachidonic acid in tissues to normalize endocannabinoid tone. Obesity incidence continues to escalate as a global nutrition and health problem. Scientists and clinicians are engaged in numerous research approaches that include behavior, education, applied nutrition studies and clinical therapies to prevent, control and reverse obesity. The common goal is to identify areas of basic and clinical research to understand aspects of human biology that contribute to obesity. In these approaches recent discoveries in biology and advancing technologies are tools employed to prevent and reverse obesity. The purpose of this review article is to present the current knowledge of key components of the endocannabinoid system that contribute to eating, influence systemic energy metabolism, and dietary factors that alter the responses of ligand binding and activation of cannabinoid receptors. Herein the objectives are to (1) describe the relationship between dietary polyunsaturated fatty acids (PUFA) and obesity, (2) explain the role of this signaling system in obesity, and (3) present areas of consequential future research with dietary long chain PUFA. There are several gaps in the knowledge of the role dietary PUFA play in the tone of the endocannabinoid signaling system involving ligands and receptors. Elucidating the PUFA relationship to signaling tone may explain the presumed overstimulation of signaling believed to contribute to over eating, fat accretion and inflammation. Future research in this endeavor must be hypothesis driven utilizing appropriate models for investigations on dietary PUFA, endocannabinoids and obesity.