Abstract
Lifestyle is a well-known environmental factor that plays a major role in facilitating the development of metabolic syndrome or eventually exacerbating its consequences. Various lifestyle factors, especially changes in dietary habits, extreme temperatures, unusual light–dark cycles, substance abuse, and other stressful factors, are also established modifiers of the endocannabinoid system and its extended version, the endocannabinoidome. The endocannabinoidome is a complex lipid signaling system composed of a plethora (>100) of fatty acid-derived mediators and their receptors and anabolic and catabolic enzymes (>50 proteins) which are deeply involved in the control of energy metabolism and its pathological deviations. A strong link between the endocannabinoidome and another major player in metabolism and dysmetabolism, the gut microbiome, is also emerging. Here, we review several examples of how lifestyle modifications (westernized diets, lack or presence of certain nutritional factors, physical exercise, and the use of cannabis) can modulate the propensity to develop metabolic syndrome by modifying the crosstalk between the endocannabinoidome and the gut microbiome and, hence, how lifestyle interventions can provide new therapies against cardiometabolic risk by ensuring correct functioning of both these systems.
Highlights
Diets poor in essential nutritional factors and rich in high-calorie nutrients, lack of exercise, and uncontrolled use of recreational substances or certain therapeutic drugs, together with other environmental challenges such as recently changed lifestyle habits in populations living at extreme temperatures or regarding night–day cycles, are all known to negatively affect the body’s ability to regulate energy metabolism and, contribute to the development of metabolic syndrome [1]
Endocannabinoids and endocannabinoidome mediators are derived from long-chain fatty acids, and it is predictable that prolonged diets rich in some fatty acids rather than others can affect the tissue concentrations of these molecules in as much as they can change the fatty acid composition of phospholipids acting as biosynthetic precursors [12,13]
If one considers that gut microbiota composition is altered by the same dietary and environmental factors and unhealthy behaviors that affect the endocannabinoid system [20,22,23,24], it is perhaps not so farfetched to suggest that the lifestyle–gut microbiome–endocannabinoidome triangle plays a crucial role in the development of metabolic syndrome
Summary
Diets poor in essential nutritional factors (e.g., dietary fibers or vitamins) and rich in high-calorie nutrients, lack of exercise, and uncontrolled use of recreational substances or certain therapeutic drugs, together with other environmental challenges such as recently changed lifestyle habits in populations living at extreme temperatures or regarding night–day cycles, are all known to negatively affect the body’s ability to regulate energy metabolism and, contribute to the development of metabolic syndrome [1]. There is evidence that pre- and probiotics can produce beneficial effects partly mediated by endocannabinoidome mediators, pointing to the possibility that at least some of the numerous physiological and pathological actions respectively displayed by a healthy or disrupted gut microbiota (known as dysbiosis) may be due to changes in this complex system of lipid chemical signals, both at the central nervous system and peripheral tissue level This seems to be true in the context of metabolic control in which the intestinal flora, like the endocannabinoidome, is known to play a major role [14,15,16]. We shall discuss several ways through which lifestyle-induced alterations of the endocannabinoidome—very often through direct or indirect effects on the gut microbiome (μB; that is the ensemble of genes, proteins, and metabolites provided by intestinal microorganisms)—can either worsen or ameliorate energy metabolism in mammals and, influence the development of the metabolic syndrome
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