Polymorphism rs1761667 in the CD36 Gene Is Associated to Changes in Fatty Acid Metabolism and Circulating Endocannabinoid Levels Distinctively in Normal Weight and Obese Subjects

Abstract

The multifunctional CD36 scavenger receptor facilitates fatty acid (FA) uptake and oxidation and it has been involved in the pathophysiology related to dysfunctional FA metabolism. The common variant in the CD36 gene, rs1761667 (A/G), whose allele A is characterized by a reduced protein expression, has been associated with taste sensitivity to and preference for fat. We therefore aimed at evaluating whether the CD36 polymorphism may influence fatty acid metabolism and endocannabinoid biosynthesis in normal weight (NW) and obese (OB) subjects. Red blood cell (RBC) fatty acid composition, and plasma endocannabinoid levels were determined. In NW subjects with AA genotype was found a marked reduction of RBC saturated fatty acids and palmitic/linoleic ratio (PA/LA), considered as de novo lipogenesis (DNL) biomarkers. Remarkably, to the reduction of DNL biomarkers corresponded an increase of omega-6 index, an indirect marker of the impact on fatty acid metabolism of dietary omega-6 fatty acids, endocannabinoid levels and a higher waist/hip ratio. The presence of the G allele was instead associated with increased endocannabinoid plasma levels and a trend for increased waist/hip ratio in obese subjects, even though exhibited decreased BMI with respect to those with AA genotype. These data indicate that the CD36 polymorphism, rs1761667, leads to a distinct metabolic pattern in NW and in OB subjects. Therefore, their determination may be crucial in developing personalized therapeutic strategies for ameliorating dyslipidemia and other metabolic disorders.

The CD36-PPARγ Pathway in Metabolic Disorders

“…Patients also demonstrated signs of cardiomyopathy, probably due to impaired uptake of long-chain fatty acids essential to maintaining normal heart function. Population studies have also identified several CD36 polymorphisms linked to increased risk of metabolic syndrome, acute myocardial infarction and type 2 diabetes [ 81 , 94 , 95 , 96 , 97 , 98 ], which might support their determination in the context of personalized therapeutic strategies. In particular, polymorphisms found to impair LDL-binding domain of CD36 were correlated with increased cardiovascular risk factors and unstable plaque formation.…”

Effects of CD36 Genotype on Oral Perception of Oleic Acid Supplemented Safflower Oil Emulsions in Two Ethnic Groups: A Preliminary Study

“…In particular, the substitution of A for G in the rs1761667 single nucleotide polymorphism (SNP) has been shown to decrease expression of this protein (Love‐Gregory et al., ) and associate with a reduced ability to detect fatty acids orally (Melis, Sollai, Muroni, Crnjar, & Barbarossa, ; Mrizak et al., ; Pepino, Love‐Gregory, Klein, & Abumrad, ). Recent evidence also suggests that this polymorphism is differentially associated with plasma lipid markers, such as endocannabinoid levels, and body composition in lean and obese individuals (Melis et al., ).…”

Effect of chemical interaction between oleic acid and L-Arginine on oral perception, as a function of polymorphisms of CD36 and OBPIIa and genetic ability to taste 6-n-propylthiouracil

“…Several studies showed that variations in fat perception and obesity are associated with common variants in CD36 gene [ 8 , 16 , 17 ]. In particular, several data showed that the polymorphism rs176166 (A/G), whose allele A is characterized by a decreased protein expression, could explain individual variations in fat orosensory perception [ 18 – 20 ], as well as the different metabolic pattern found between lean and obese subjects [ 21 ].…”