The cornerstones of good health are exercise, proper food, and sound nutrition. Physical exercise should be a lifelong routine, supported by proper food selections to satisfy nutrient requirements based on energy needs, energy management, and variety to achieve optimal metabolism and physiology. The human body is sustained by intermediary and systemic metabolism integrating the physiologic processes for cells, tissues, organs, and systems. Recently, interest in specific metabolites, growth factors, cytokines, and hormones called exerkines has emerged to explain cooperation between nutrient supply organs and the brain during exercise. Exerkines consist of different compounds described as signaling moiety released during and after exercise. Examples of exerkines include oxylipin 12, 13 diHOME, lipid hormone adiponectin, growth factor BDNF, metabolite lactate, reactive oxygen species (ROS), including products of fatty acid oxidation, and cytokines such as interleukin-6. At this point, it is believed that exerkines are immediate, fast, and long-lasting factors resulting from exercise to support body energy needs with an emphasis on the brain. Although exerkines that are directly a product of macronutrient metabolism such as lactate, and result from catabolism is not surprising. Furthermore, other metabolites of macronutrient metabolism seem to be candidate exerkines. The exerkines originate from muscle, adipose, and liver and support brain metabolism, energy, and physiology. The purpose of this review is to integrate the actions of exerkines with respect to metabolism that occurs during exercise and propose other participating factors of exercise and brain physiology. The role of diet and macronutrients that influence metabolism and, consequently, the impact of exercise will be discussed. This review will also describe the evidence for PUFA, their metabolic and physiologic derivatives endocannabinoids, and oxylipins that validate them being exerkines. The intent is to present additional insights to better understand exerkines with respect to systemic metabolism.
Keywords: endocannabinoids; exerkines; metabolites; metabolomics; neuroinflammation; oxylipins; systemic metabolism.