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

Tomasz Charytoniuk,Hubert Zywno,Karolina Konstantynowicz-Nowicka,Klaudia Berk,Adrian Chabowski,Wiktor Bzdega,Adrian Kolakowski

doi:10.3390/ijms23063083

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.

Highlights

Endocannabinoid System and Physical Activity—A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders
Deveaux et al conducted a study on mice which indicated that the inactivation of cannabinoid receptor type 2 reduced steatosis, liver triacylglycerol concentration, and obesity-associated inflammation caused by a high-fat diet [62]
It was indicated in a study conducted on C57Bl6/J mice with high-fat diet-induced obesity (DIO) that the factor, which is widely involved in the development of hepatic Insulin resistance (IR), is increased de novo ceramides synthesis, which is mediated by endoplasmic reticulum (ER) stress-dependent activation of CB1R [87]

Summary

The Endocannabinoid System—A Brief Overview of the Key Functions and Elements

The ECS constitutes one of the most complex biological systems in the human body, creating a milieu responsible for the plethora of essential functions, including maintaining metabolic and cardiovascular homeostasis, mediating immune responses, and modulating the signaling within reward systems, as well as playing a relevant role in the brain physiology components, such as mood, cognition, and neurogenesis [11–13]. Cannabinoid receptors (CBRs), (2) endocannabinoids (eCBs)—lipid ligands of cannabinoid receptors originating from omega-3 and omega-6 polyunsaturated fatty acids, among which anandamide (N-arachidonoyl-ethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) received the most attention and were best described in the literature, (3) enzymes involved in bioformation and degradation of eCBs [15,16]. AEA constitutes a partial agonist of cannabinoid receptors synthesized from N-arachidonoyl phosphatidylethanolamine (NAPE) coordinated by N-acyl-phosphatidylethanolamine phospholipase D-like esterase (NAPE-PLD). 2022, 23, 3083 researchers provided the term “endocannabinoidome” (eCBome), which refers to the broad and expanded signaling system that, apart from the aforementioned elements, contains a large number of different membrane and nuclear receptors, i.e., PPARs, transient receptor potential vanniloid 1 ion channel (TRPV1), various GPCRs, their endogenous ligands, and dozens of enzymes playing important roles in endocannabinoid signaling. Endocannabinoidome may constitute a promising target in the therapy of various pathologies in which the components of ECS seem to be involved; further research on the emerging new metabolic implications of eCBome remains in high demand [16,17,27,28]

The Endocannabinoid System and Metabolic Pathologies

Obesity and Non-Alcoholic Fatty Liver Disease (NAFLD)

Insulin Resistance and Type 2 Diabetes

The Endocannabinoid System and Physical Activity

Conclusions