Abstract
The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity.
Highlights
The worldwide prevalence of overweight adults increased from 28.8 to 36.9% in men and from 29.8 to 38.0% in women between 1980 and 2013 [1]
We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk
Endocannabinoids play an important role in these mechanisms. They are membrane phospholipid-derived mediators that act as endogenous ligands on the two known cannabinoid receptors (CB1 and CB2) that are present in the central nervous system and in the peripheral tissues and organs of many species [7]
Summary
The worldwide prevalence of overweight adults (body mass index [BMI] of 25 kg/m2 or greater) increased from 28.8 to 36.9% in men and from 29.8 to 38.0% in women between 1980 and 2013 [1]. The mechanism of obesity-induced major health issues is chronic inflammation in the white adipose tissue [5], and the development of white adipose tissue dysfunction. This may affect lipid handling and contribute to excessive fat accumulation in non-adipose tissues [6]. Endocannabinoids (eCBs) play an important role in these mechanisms. They are membrane phospholipid-derived mediators that act as endogenous ligands on the two known cannabinoid receptors (CB1 and CB2) that are present in the central nervous system and in the peripheral tissues and organs of many species [7]. The eCBs are primarily inactivated by cellular reuptake and intracellular hydrolysis by the enzyme fatty acid amide hydrolase (FAAH)—mostly for AEA—and monoacylglycerol lipase, that is selective for 2-AG [10]
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