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CD36 genotype and long-chain fatty acid uptake in the heart
Taigo Kintaka1, Takao Tanaka, Makoto Imai
1Department of Internal Medicine, Osaka Medical College,Takatsuki, Japan.
Insights
A single CD36 gene mutation (CD36+/-) significantly reduces long-chain fatty acid (LCFA) uptake in the heart, similar to CD36-/-. This highlights CD36
Area of Science:
- Cardiology
- Genetics
- Metabolism
Background:
- CD36 gene mutations (CD36-/-) cause severe defects in cardiac long-chain fatty acid (LCFA) uptake.
- The impact of a single CD36 gene mutation (CD36+/-) on LCFA uptake remained unknown.
Purpose of the Study:
- To evaluate the effect of CD36 genotype (wild-type, CD36+/-, CD36-/-) on cardiac LCFA uptake.
- To determine if CD36 genotype influences LCFA uptake independently of heart disease.
Main Methods:
- Genotyping of the CD36 gene in 29 subjects.
- Assessment of CD36 protein expression via flow cytometry.
- Quantification of cardiac LCFA uptake using Iodine-123 fatty acid imaging (H/M ratio).
Main Results:
- Cardiac LCFA uptake (H/M ratio) was significantly reduced in both CD36+/- (1.90) and CD36-/- (1.40) subjects compared to wild-type (2.28).
- Reduced LCFA uptake in CD36+/- and CD36-/- groups was observed irrespective of heart disease presence.
- No significant difference in H/M ratios between healthy individuals and heart disease patients within the same CD36 genotype group.
Conclusions:
- A single CD36 gene mutation (CD36+/-) significantly impairs myocardial LCFA uptake.
- CD36 genotype is a key determinant of cardiac LCFA uptake, independent of heart disease.
- This finding suggests a fundamental role for CD36 in regulating heart fatty acid metabolism.
Abstract:
Homozygous or compound heterozygous mutation of the CD36 gene (CD36-/-) in humans results in severe defects of the uptake of long-chain fatty acids (LCFAs) in the heart. Because the effect of a single mutation of this gene (CD36+/-) on the LCFA uptake is not known, it was evaluated in 29 subjects with the CD36 wild-type gene (WT) (6 healthy subjects, 10 patients with heart disease), CD36+/- (4 healthy subjects, 5 patients) and CD36-/- (4 patients). The CD36 genotype was identified in the coding region of genomic DNA, and the expression of CD36 protein was examined by flow cytometry after staining with monoclonal anti-CD36 antibody. The LCFA uptake in the heart was assessed as the radioactivity accumulation ratio of heart to mediastinum after intravenous administration of iodine-123 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (H/M ratio). The H/M ratios in WT, CD36+/- and CD36-/- were 2.28 +/- 0.10, 1.90 +/- 0.06 and 1.40 +/- 0.11, respectively (p < 0.0001, among groups). The H/M ratio between healthy subjects and patients with heart disease for WT and CD36+/- did not differ significantly (ie, those of WT and CD36+/- in healthy subjects and patients were 2.29 +/- 0.08 vs 2.27 +/- 0.12 and 1.90+/- 0.07 vs 1.89 +/- 0.05, respectively). Not only CD36-/- but also CD36+/- resulted in a significant reduction of the LCFA uptake in the heart independent of heart disease, suggesting genotype dependency and that CD36 might be a fundamental determinant of myocardial LCFA uptake.