Genetic polymorphisms of the endocannabinoid system in obesity and diabetes

Abstract

The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to examine the contribution of single nucleotide polymorphisms (SNPs) of the ECS to adiposity and glucose metabolism. Database searches identified 734 articles, of which 65 were included; these covered 70 SNPs in genes coding for cannabinoid receptors 1 and 2 (CB , CB ), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). No studies included SNPs relating to monoacylglycerol lipase or diacylglycerol lipase. The CB receptor SNP rs1049353 showed 17 associations with lower body mass index (BMI) and fat mass (five studies). It also showed three associations with lower insulin levels (one study). Conversely, the CB receptor SNP rs806368 was associated with increased BMI and waist circumference (two studies). The FAAH SNP rs324420 was associated with increased obesity (three studies). A haplotype of NAPE-PLD was associated with decreased BMI (one study). A total of 60 SNPs showed no association with any measured outcome. This review suggests a complex but important role of ECS SNPs in energy and glucose metabolism.

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

“…When the CB2 receptor is selectively stimulated with JWH-133, this critical condition is restored in primary cultures of adipocytes obtained from obese subjects [93,98,99]. Another polymorphism positively associated with obesity is the FAAH polymorphism rs324420 that reduces FAAH activity, leading to higher AEA levels and consequent over-activation of CB1 receptors, which, in turn, causes adipogenesis and a high obesity risk [100,101]. The secretion of pro-inflammatory mediators by adipose tissue can increase the risk of developing secondary pathologies, such as type 2 diabetes, cardiovascular diseases, cancer, and non-alcoholic fatty liver disease (NAFLD) [102].…”

The gut microbiome, endocannabinoids and metabolic disorders

“…Such alterations may be normalised following weight loss-inducing interventions, such as caloric restriction and exercise (Di Marzo et al 2009) or bariatric surgery (Azar et al 2019). The presence of polymorphisms in the genes encoding for eCB receptors and anabolic or catabolic enzymes (Martins et al 2015, Doris et al 2019, Thethi et al 2020) may also underlie eCB system dysregulation in obesity.…”

The Relationship between Selected CNR1, MC4R, LEP, FTO and VDR Gene Polymorphisms and Several Basic Toxicological Parameters Among Persons Occupationally Exposed to Arsenic, Cadmium and Lead

“…Until now, we were unable to find other studies showing correlations between CNR1 polymorphism locus rs1049353 and arsenic concentration. Moreover, data concerning this polymorphism and its correlation with BMI parameters are inconclusive and often contradictory [7]. In our research we were able to determine a significant correlation: allele G is correlated with higher arsenic concentration.…”

“…Several specific single nucleotide polymorphisms of the CNR1 gene (located in 6q15) were found (rs806381, rs806368, rs1049353, rs12720071), as well as several possible combinations. The most popular, A to G transition in rs1049353, leads to higher body mass index and wider waist circumference [7]. Another studied polymorphism was leptin (LEP), a hormone made mostly by adipocyte cells.…”