The Endocannabinoid System and Physical Activity—A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders

Abstract

Rapidly increasing worldwide prevalence of obesity and related pathologies encompassing coronary heart disease, hypertension, metabolic syndrome, or type 2 diabetes constitute serious threats to global health and are associated with a significantly elevated risk of premature death. Considering the enormous burden of these pathologies, novel therapeutic and preventive patterns are indispensable. Dysregulation of one of the most complex biological systems in the human body namely, the endocannabinoid system (ECS) may result in metabolic imbalance and development of insulin resistance, type 2 diabetes, or non-alcoholic fatty liver disease. Furthermore, many studies showed that physical exercises, depending on their type, intensity, and frequency, exert various alterations within the ECS. Emerging evidence suggests that targeting the ECS via physical activity may produce robust beneficial effects on the course of metabolic pathologies. However, the data showing a direct correlation between the ECS and physical activity in the aspect of metabolic health are very scarce. Therefore, the aim of this review was to provide the most up-to-date state of knowledge about the interplay between the ECS activity and physical exercises in the novel therapeutic and preventive approach toward metabolic pathologies. We believe that this paper, at least in part, will fulfill the existing gap in knowledge and encourage researchers to further explore this very complex yet interesting link between the ECS, its action in physical activity, and subsequent positive outcomes for metabolic health.

Quantal size increase induced by the endocannabinoid 2‐arachidonoylglycerol requires activation of CGRP receptors in mouse motor synapses

“…The specific and peculiar role of ECs in neuromuscular junctions gains great attention (Balezina et al., 2021; Behl et al., 2022; Dalle et al., 2022; Ge et al., 2020; Morsch et al., 2018; Tarasova, Khotkina, Gaydukov, et al., 2021) but still remains poorly studied up to date. Despite the relatively low density of CB1 receptors on muscle membranes, their activation by ECs plays a significant role in muscle metabolism and homeostasis (Alger, 2013; Charytoniuk et al., 2022; Dalle et al., 2022). This may be accompanied by the influence of ECs on nerve terminals to provide the release of important trophic factors, such as CGRP, to maintain and stabilize synaptic transmission and muscle contractions (Andersen & Clausen, 1993; Machado et al., 2019; Sala et al., 1995; Uchida et al., 1990; Takami et al., 1985).…”

Sex differences in endocannabinoids during 3 years of Mediterranean diet intervention: Association with insulin resistance and weight loss in a population with metabolic syndrome

“…This may be due to the greater intensity of the dietary component (individual counseling visits and free provision of EVOO and mixed nuts) compared to the physical activity component (based on recommendations delivered by dietitians) of the Predimed-Plus study ( 39 ). Therefore, it is more likely that changes in eCBs and NAEs during the Predimed-Plus lifestyle intervention were due to the cardiometabolic effects of the MedDiet component than to those of the physical activity component, although some studies have already reported the modulation of eCBs by physical activity (mainly after acute exercise) ( 82 ).…”

The Involvement of Lipid Mediators in the Mechanisms of Exercise-Induced Muscle Damage

“…The two most studied eCBs are N-arachidonoylethanolamine (AEA) and arachidonoylglycerol (2-AG). AEA is a ligand for the CB1R while 2-AG is a ligand for both CB 1 and CB 2 receptors [49][50][51].…”

“…There are some studies that have investigated the influence of physical activity and/or exercise on the endocannabinoid signaling, though the mechanisms are still unclear. Physical activity depending on factors, such as type, frequency, intensity, duration, subject's age and gender can lead to the activation of the ECS, increasing the levels of AEA and 2-AG in the circulation and altering the levels of the CBRs [50,51]. The CBS activation positively affects many systems and tissues, including the central nervous system (e.g., anti-depressive properties, memory and mood improvement, increased neurogenesis and neuroplasticity), cardiovascular system (e.g., reduction in blood pressure, increased endothelial function), respiratory system (bronchodilation), digestive system (e.g., increase in insulin sensitivity, reduction in insulin resistance, reduction in leptin resistance), as well as the function of adipocytes (e.g., increased lipolysis, reduced lipogenesis and increase in adiponectin).…”