Dataset Information

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.

SUBMITTER: Melis M

PROVIDER: S-EPMC5724198 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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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.

Melis Melania M Carta Gianfranca G Pintus Stefano S Pintus Paolo P Piras Carla A CA Murru Elisabetta E Manca Claudia C Di Marzo Vincenzo V Banni Sebastiano S Tomassini Barbarossa Iole I

Frontiers in physiology 20171206

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 endoca ...[more]

PMID: 29270130

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Project description:BACKGROUND: Dyslipidemia is a common metabolic disorder that may result from abnormalities in the synthesis, processing and catabolism of lipoprotein particles. Disorders of lipoprotein concentrations and elevated concentration of oxidized lipoproteins (oxLDL) are risk factors in the pathogenesis of cardiovascular diseases (CVD). CD36 plays an important role in lipid metabolism and polymorphisms in the CD36 gene are related to cardiovascular risk factors. The purpose of this study was to evaluate whether there is an association between genotypes and haplotypes of five polymorphisms in the CD36 gene with lipid levels in young normal-weight subjects. METHODS: A total of 232 unrelated subjects with normal-weight of 18 to 25 years old (157 women and 75 men) were randomly selected. The lipid profile and glucose levels were measured by enzymatic colorimetric assays. Genotyping of the polymorphisms -33137A/G (rs1984112), -31118G/A (rs1761667), -22674 T/C (rs2151916), 27645 Ins/Del (rs3840546) and 30294G/C (rs1049673) in the CD36 receptor gene was performed by polymerase chain reaction and restriction fragment length polymorphism, linkage disequilibrium analysis among the five polymorphisms and an analysis of haplotype were estimated. RESULTS: HDL-C levels was lower in men than in women (P =?0.03). However, the median oxLDL levels in men was higher than in women (P =?0.05). There was no significant difference in the levels of TC, TG, LDL-C and glucose (P >?0.05). HDL-C levels were lower in the subjects with TC genotype of polymorphism -22674 T/C (P =?0.04), but the carriers of TT genotype had lower oxLDL levels (P =?0.01). LDL-C levels were higher in young carriers of CC genotype for 30294G/C polymorphism than non-carriers (P =?0.03). The subjects carrying the AATDC haplotype had 3.2 times presumably higher risk of LDL-C >?100 mg/dL than the carrying the AGTIG haplotype (P =?0.02), whereas the subjects carrying the AATIC haplotype had 2.0 times presumably higher risk of TC >?200 mg/dL than the carrying the AGTIC haplotype (P =?0.02). CONCLUSION: The study provides evidence of a genetic association of CD36 haplotypes with the variability in LDL-C and TC levels in a sample of normal-weight subjects.

Project description:Abstract Objectives Nonalcohol fatty liver disease (NAFLD) is one of the considerable health problems in the world. NAFLD is a representative phenotype in the liver reflecting individual's lifestyle. Previous studies suggested that a single nucleotide polymorphism (SNP) in the CD36 gene was associated with dietary fat intake and fat metabolism. Therefore, we hypothesized that this SNP may be associated with fatty liver (FL) and NAFLD. We conducted this cross-sectional study to examine the association between two CD36 polymorphisms (rs1761667 and rs1527483) and FL and NAFLD in a Japanese population. Methods A total of 525 local residents participated in the health check-up in Yakumo town, Hokkaido, Japan. This cross-sectional study was conducted based on clinical information collected in this health check-up. Among all participants, 57 people were excluded due to the inadequate informed consent, clinical history of liver disease. Genotyping of two polymorphisms in the CD36 gpgbrkkene was performed by using the PCR-CTPP method. Ultrasound examination was performed by four qualified ultrasonographers. In this present, NAFLD was defined as 1) presence of FL and 2) a daily alcohol consumption <10 g in women and <20 g in men. Multivariable regression analysis was performed after adjusting for age, sex, waist circumference, medicine for dyslipidemia. Results The mean age of participants was 63.4 (10.0). The minor allele frequency of rs1761667 and rs1527483 was 0.26 and 0.21, respectively. The presence of FL and NAFLD was 90 (19.2%) and 67 (14.3%), respectively. Multiple regression analyses showed a significant association between rs1761667 and presence of FL (P = 0.04), and FL grade (P = 0.03). However, rs1761667 was not significantly associated with NAFLD (P = 0.11). No significant associations were found between rs1527483 and FL and NAFLD. Conclusions A polymorphism (rs1761667) in the CD36 gene was associated with the presence of FL, but we did not find a significant association between this SNP and NAFLD. Funding Sources This study was supported by the Mishima Kaiun Memorial Foundation.

Project description:BackgroundIncreasing evidence supports a relationship between obesity and either infertility or subfertility in women. Most previous omics studies were focused on determining if the serum and follicular fluid expression profiles of subjects afflicted with both obesity-related infertility and polycystic ovary syndrome (PCOS) are different than those in normal healthy controls. As granulosa cells (GCs) are essential for oocyte development and fertility, we determined here if the protein expression profiles in the GCs from obese subjects are different than those in their normal-weight counterpart.MethodsGC samples were collected from obese female subjects (n = 14) and normal-weight female subjects (n = 12) who were infertile and underwent in vitro fertilization (IVF) treatment due to tubal pathology. A quantitative approach including tandem mass tag labeling and liquid chromatography tandem mass spectrometry (TMT) was employed to identify differentially expressed proteins. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then conducted to interrogate the functions and pathways of identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in both groups.ResultsA total of 228 differentially expressed proteins were noted, including 138 that were upregulated whereas 90 others were downregulated. Significant pathways and GO terms associated with protein expression changes were also identified, especially within the mitochondrial electron transport chain. The levels of free fatty acids in both the serum and follicular fluid of obese subjects were significantly higher than those in matched normal-weight subjects.ConclusionsIn GCs obtained from obese subjects, their mitochondria were damaged and the endoplasmic reticulum stress response was accompanied by dysregulated hormonal synthesis whereas none of these changes occurred in normal-weight subjects. These alterations may be related to the high FFA and TG levels detected in human follicular fluid.

Dataset Information

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.

Publications

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

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