Dietary PUFA and Exercise Dynamic Actions on Endocannabinoids in Brain – Consequences for Neural Plasticity and Neuroinflammation

The brain and peripheral nervous system provide oversight to muscle physiology and metabolism. Muscle is the largest organ in the body and critical for glucose sensitivity, prevention of diabetes, and control of obesity. The CNS produces endocannabinoids (eCBs) that play a role in brain neurobiology, such as inflammation and pain. Interestingly, studies in humans and rodents show that moderate duration of exercise increases eCBs in the brain and blood and influences cannabinoid receptors. Cannabinoid actions in the nervous system have advanced our understanding of pain, well-being, and disease. Nutrition is an important aspect of brain and eCB physiology because polyunsaturated fatty acids (PUFAs) are biosynthesized to the eCBs. The primary eCB metabolites are derived from arachidonic acid, an n-6 PUFAs, and the n-3 PUFAs, eicosapentaenoic and docosahexaenoic acids. The eCBs bind to cannabinoid receptors CB1 and CB2 to exert a wide range of activities, such as stimulate appetite, influence energy metabolism, support the immune system, and facilitate neuroplasticity. A diet containing different essential n-6 and n-3 PUFAs will dominate the formation of specific eCBs, and subsequently, their actions as ligands to CB1 and CB2. The eCB also function in a substrate role for COX enzymes, including potential substrates for the oxylipins (OxLs), which can be pro-inflammatory. Together, the eCBs and OxLs act as modulators of neuroinflammation. Thus, dietary PUFAs have implications in exercise responses as in the synthesis of eCBs and their effects on neuroinflammation. Neurotrophins are another participant in the diet and eCB interactions, specifically the brain-derived neurotrophic factor (BDNF). Particularly, BDNF supports neuroplasticity in cooperation with the endocannabinoid system (ECS). This review will present the role of PUFA in eCB biosynthesis, discuss the ECS and OxLs in neuroinflammation, highlight the evidence of exercise effects on eCBs, and describe eCBs and BDNF actions on neuroplasticity.