CD36 Genotype and Long-Chain Fatty Acid Uptake in the Heart.

Abstract

lthough the heart preferentially uses long-chain fatty acids (LCFAs) as its main energy substrate, alteration in LCFA utilization is well known in pathological hearts 1 and in such cases, assessment of the LCFA metabolism is of clinical importance in determining etiology and developing therapeutic strategies.LCFA metabolism in the heart has been clinically evaluated by scintigraphy using iodine-123-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP), a radioactive LCFA analog. Regional defects of myocardial LCFA uptake are often revealed in patients with coronary artery disease 2-5 and have been interpreted as follows: (1) dissociation between BMIPP and flow-tracer activity (ie, reduced BMIPP uptake but less reduced flow-tracer accumulation) may indicate ischemic but still viable myocardium (ie, the 'mismatch of blood flow and metabolism'); or (2) diminished accumulation of BMIPP together with reduced flowtracer radioactivity related to necrotic or fibrotic tissue.However, despite the increase of flow tracer accumulation in the heart, defects of BMIPP uptake have been noticed in patients with hypertrophic cardiomyopathy and interestingly, an almost negative depiction of the heart by BMIPP scintigraphy has been occasionally observed in patients without discernible defects of coronary perfusion. [6][7][8] The underlying mechanism of this discrepancy (ie, decreased uptake of LCFA in the heart despite rather increased uptake of flow-tracer) has not been fully elucidated. Circulation Journal Vol.66, September 2002The first step of cellular LCFA metabolism is a transverse process of LCFA in the plasma membrane. Although this process is still in dispute, several lines of evidence suggest a protein-mediated process in addition to a simple diffusive process. Among the putative proteins involved, CD36 is a potential candidate. [8][9][10][11] In fact, CD36 knock-out mice have severe defects of LCFA uptake in the heart, 10 and homozygous and compound heterozygous mutation of the CD36 gene (hereafter referred to as CD36 -/-) in humans also causes severe defects of myocardial LCFA uptake, with an almost negative depiction of the heart by BMIPP scintigraphy. 8 In addition to the effects of CD36 -/-on the LCFA uptake in the heart, CD36 -/-resulted in a lack of CD36 expression in platelets and monocytes, referred to as type I CD36 deficiency. 12 We recently found a strong association between the genotype in the coding region of CD36 and the expression level of CD36. Heterozygous mutations in the coding region of this gene (hereafter referred to as CD36 +/-) resulted in the reduced expression of CD36 in monocytes, approximately half that observed in the wild-type gene (hereafter referred to as WT). 13 Accordingly, we hypothesized that not only CD36 -/-but also CD36 +/-might lead to the defects of LCFA uptake in the heart.The effects of CD36 -/-on the LCFA uptake in the heart have been characterized, so far, only qualitatively; that is, an almost negative depiction of the heart by BMIPP scintigraphy. The quantitative evaluat...

FAT/CD36 is localized in sarcolemma and in vesicle-like structures in subsarcolemma regions but not in mitochondria

“…Furthermore, the role of FAT/CD36 in LCFA plasma membrane transport is supported by studies reporting decreased LCFA uptake in cardiac muscle from humans who exhibit partial or total defi ciency in FAT/CD36 protein ( 48,49 ) and in cardiac and skeletal muscle from CD36 null mice ( 50,51 ). In the present study, we did not observe differences in total FAT/CD36 and FABPpm protein expression between lean and obese Zucker rats ( Fig.…”

Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

“…The mouse hindlimb muscles were removed and dissected free of connective tissue, nervous tissue, and visible fat. The muscles were minced and homogenized on ice three times (5 s each) using a Polytron by guest, on May 10, 2018 www.jlr.org Downloaded from size 10-15 kDa), 550 µM palmitate, 542 nM [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitic acid (PerkinElmer), and 6 mM glucose. The perfusion apparatus included an artifi cial lung by means of which the arterial perfusate was continuously gassed with a mixture of 95% O 2 /5% CO 2 .…”

“…Isometric muscle contractions were induced by stimulating the sciatic nerve electrically, as previously described ( 30,31 ), with supramaximal trains 5-15 V adjusted to obtain full fi ber recruitment, 50 Hz with impulse duration of 1 ms, delivered every 3 s. Muscles were stimulated to contract for 1 or 10 min. FA uptake and FA oxidation, 14 C and 14 CO 2 radioactivities, respectively, were determined in duplicate, as previously described in detail ( 32,33 ). P CO2 , P O2 , and pH were measured with an ABL-5 analyzer (Radiometer America; Westlake, OH).…”

“…C]palmiate oxidation to 14 CO 2 [reported elsewhere ( 27 )] and incorporation of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitic acid into triacylglycerol (TG) and diacylglycerol (DG) in the muscles, as described previously ( 24 ). For FA oxidation experiments, gaseous 14 CO 2 was liberated from the incubation media with 1 M acetic acid and trapped with vials containing 0.5 ml benzethonium hydroxide (Sigma; St. Louis, MO).…”

Influence of CD36 Deficiency on Heart Disease in Children

“…Kitanaka et al reported that the uptake of LCFA in the heart was strongly associated with the CD36 genotype, independent of the heart disease, and that the type II CD36-deficient phenotype did not always accompany a defect in myocardial LCFA uptake. 23 The partially reduced myocardial uptake of BMIPP in the present patients may be related to CD36 deficiency type II.…”