Lifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome

Vincenzo Di Marzo, Cristoforo Silvestri, Vincenzo Di Marzo, Cristoforo Silvestri

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.

Keywords: endocannabinoidome; endocannabinoids; metabolic syndrome; microbiome.

Conflict of interest statement

The authors receive research grants from GW Pharmaceuticals, not related to this work.

Figures

Figure 1
Figure 1
Endocannabinoidome mediators and their receptors (A) and anabolic and catabolic enzymes (B). Interactions are indicated by dark shaded boxes, and anabolic enzymes that function in concert are grouped together; “X” indicates inhibitory interactions; “a” indicates that enzymes only function with arachidonoyl homologs. A lighter shade of gray indicates a lower interaction with the receptors or a lesser role of the enzymes in biosynthesis or degradation.
Figure 2
Figure 2
The endocannabinoidome–microbiome axis as a mechanism through which lifestyle choices affect various aspects of metabolism, which in turn may lead to the metabolic syndrome when dysregulated. This can, in turn, impact on both endocannabinoidome and microbiome-mediated signaling and, ultimately, also on lifestyle, thus creating potential vicious circles.

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