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.
Highlights
The multifunctional CD36 scavenger receptor is an 88kDa membrane glycosilated protein of 471 amino acid which has been originally identified in platelet membrane (Ikeda et al, 1989)
Molecular analysis at the rs1761667 (A/G) polymorphism of CD36 identified in the group of normal weight (NW) seven subjects being homozygous AA, 39 heterozygous AG, and 18 homozygous GG, while in OB, 15 subjects were homozygous AA, 31 heterozygous AG, and 16 homozygous GG
A pairwise comparison showed that the waist/hip ratio of homozygous AA and NW subjects was significantly higher than that of NW subjects that were heterozygous or homozygous for the G-allele (p < 0.040, Duncan test), and not significantly different from that determined in OB subjects with the same genotype, who exhibited values not different from those of other genotype groups of OB subjects (Figure 1B)
Summary
The multifunctional CD36 scavenger receptor is an 88kDa membrane glycosilated protein of 471 amino acid which has been originally identified in platelet membrane (Ikeda et al, 1989). CD36 expression in circumvallate papillae has been found to be significantly decreased in high-fat diet-induced obese rats (Zhang et al, 2011) This suggested that decreased expression of CD36 diminishes sensitivity to fat taste, leading to increase fatty food intake as a compensatory reaction. The presence of CD36 has been found in gustatory papillae in humans (Simons et al, 2011; Ozdener et al, 2014) as the main long-chain fatty acid receptor in taste bud cells, contributing to the orosensory perception of dietary lipid and fat preference (Keller et al, 2012; Pepino et al, 2012). Since circulating levels of endocannabinoids are strongly associated to visceral obesity, less efficient mitochondrial function and ectopic fat deposition (Cristino et al, 2014), these results suggested that PROP taste sensitivity may predispose to metabolic changes and thereby body mass composition. Due to the relevant influence of the CD36 polymorphism rs1761667 on macronutrient preference and cellular lipid metabolism in humans, we aimed at evaluating whether it may impact fatty acid metabolism and endocannabinoid biosynthesis in NW and OB subjects
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