What Role Does the Endocannabinoid System Play in the Pathogenesis of Obesity?

Abstract

The endocannabinoid system (ECS) is an endogenous signaling system formed by specific receptors (cannabinoid type 1 and type 2 (CB1 and CB2)), their endogenous ligands (endocannabinoids), and enzymes involved in their synthesis and degradation. The ECS, centrally and peripherally, is involved in various physiological processes, including regulation of energy balance, promotion of metabolic process, food intake, weight gain, promotion of fat accumulation in adipocytes, and regulation of body homeostasis; thus, its overactivity may be related to obesity. In this review, we try to explain the role of the ECS and the impact of genetic factors on endocannabinoid system modulation in the pathogenesis of obesity, which is a global and civilizational problem affecting the entire world population regardless of age. We also emphasize that the search for potential new targets for health assessment, treatment, and the development of possible therapies in obesity is of great importance.

Beneficial Changes in Rat Vascular Endocannabinoid System in Primary Hypertension and under Treatment with Chronic Inhibition of Fatty Acid Amide Hydrolase by URB597

“…Importantly, all of the above effects of URB597 were noticed in SHR but not in their normotensive controls. Similarly, the enhancement of the vasodilatory effect of Ach in the presence of increased endogenous or exogenous (i.e., cannabidiol) cannabinoids has previously been demonstrated in diabetic and hypertensive rats, but not in lean or normotensive control animals [ 1 , 37 , 38 ]: that is, only in the case of increased endocannabinoid levels and vascular dysfunction (for a review, see [ 1 , 2 , 39 ]). This is consistent with the known pro-homeostatic properties of the endocannabinoid system, which plays a crucial role in a perturbed system, but not in a healthy one.…”

Potential of Fatty Acid Amide Hydrolase (FAAH), Monoacylglycerol Lipase (MAGL), and Diacylglycerol Lipase (DAGL) Enzymes as Targets for Obesity Treatment: A Narrative Review

“…The ECS has a multi-faceted role in the control of food intake and body weight, and it acts through both peripheral and central mechanisms. In the periphery, activation of CB1 receptors (e.g., by binding of AEA or 2-AG) promotes fat storage in adipocytes and increases lipogenesis, increases glucose uptake, and reduces satiety signals [9]. Centrally, activation of the ECS interferes with the control of hunger and satiety in multiple brain regions, including the hypothalamus and brain stem [9].…”

“…In the periphery, activation of CB1 receptors (e.g., by binding of AEA or 2-AG) promotes fat storage in adipocytes and increases lipogenesis, increases glucose uptake, and reduces satiety signals [9]. Centrally, activation of the ECS interferes with the control of hunger and satiety in multiple brain regions, including the hypothalamus and brain stem [9]. This likely involves a complex interplay between endocannabinoids and other neurotransmitters or hormones involved in hunger and satiety such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and neuropeptide Y (NPY) [9].…”

“…Centrally, activation of the ECS interferes with the control of hunger and satiety in multiple brain regions, including the hypothalamus and brain stem [9]. This likely involves a complex interplay between endocannabinoids and other neurotransmitters or hormones involved in hunger and satiety such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and neuropeptide Y (NPY) [9]. Since the primary physiological function of the ECS is thought to shift energy balance towards energy storage, overactivation of the ECS likely contributes to obesity [5].…”

“…To date, previous reviews have highlighted the genetic association between variation in the FAAH gene and obesity-related outcomes in humans [9,24]. However, no previous reviews have focused specifically on evidence for a potential role of ECS enzymes in obesity treatment.…”