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Pathophysiology/Complications

Adipose and Muscle Tissue Profile of CD36 Transcripts in Obese Subjects Highlights the Role of CD36 in Fatty Acid Homeostasis and Insulin Resistance

  1. Terri A. Pietka,
  2. Timothy Schappe,
  3. Caterina Conte,
  4. Elisa Fabbrini,
  5. Bruce W. Patterson,
  6. Samuel Klein,
  7. Nada A. Abumrad and
  8. Latisha Love-Gregory⇑
  1. Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO
  1. Corresponding author: Latisha Love-Gregory, lgregory{at}wustl.edu.
Diabetes Care 2014 Jul; 37(7): 1990-1997. https://doi.org/10.2337/dc13-2835
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    Figure 1

    Distribution of alternative CD36 first exon transcripts in human tissues and cells. A: Diagram of the CD36 gene illustrating position of the untranslated (empty boxes) CD36 first exon regions (1A–1F) relative to coding exons 3–14 (filled boxes). The bent lines illustrate splicing between the alternative first exons and exon 2. B: Relative expression of the major alternative transcripts 1A, 1B, and 1C in commercially available human tissue (adipose tissue, heart, liver, skeletal muscle, tongue, and pancreas). C: Human THP-1 monocytes and macrophages where 1B is the predominant transcript. D: HMVECs showing predominance of transcript 1D. E: Human preadipocytes and adipocytes (SGBS cell line) showing higher abundance of 1B relative to the 1A and 1C transcripts. Expression (arbitrary units) of the transcripts normalized to the human RPLPO gene is shown, and data are representative of duplicate determinations from at least two experiments. Details for differentiation of THP-1 and SGBS cells are in RESEARCH DESIGN AND Methods. AU, arbitrary units.

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    Figure 2

    CD36 common promoter SNP rs1761667 influences skeletal muscle CD36 expression and muscle glucose uptake. Expression is compared between genotype groups: (A) total skeletal muscle CD36 mRNA, (B) skeletal muscle 1B, and (C) skeletal muscle 1A. Sample size n = 12 A/A and 15 G/−. D: Insulin-stimulated muscle glucose uptake. Rs1761667 G/− genotype further impairs insulin-stimulated glucose uptake in subjects with high IHTGs. Subjects were subdivided into those having lower or higher than 5% IHTG. Rs1761667 genotype distribution in the subgroups: IHTG <5%, n = 8 A/A, and n = 17 G/–. For IHTG >5%, n = 11 A/A and n = 17 G/–; see Supplementary Table 2 for subject characteristics in the subgroups. AU, arbitrary units. *P = 0.01.

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  • Table 1

    Characteristics of the study subjects

    N (male/female)53 (15/38)
    Age, years41 ± 2
    BMI, kg/m235.9 ± 0.6
    Glucose, mg/dL94 ± 0.93
    Insulin, μIU/mL14.5 ± 1.2
    IHTG, % liver volume13 ± 2
    TGs, mg/dL136 ± 9
    Total cholesterol, mg/dL170 ± 4
    HDL cholesterol, mg/dL45 ± 2
    LDL cholesterol, mg/dL100 ± 3
    • Values are mean ± SEM unless otherwise noted.

  • Table 2

    CD36 transcripts in adipose tissue correlate positively with measures of insulin sensitivity while transcripts in skeletal correlate with FFA Rd and VLDL clearance

    Total1A1B1C
    Adipose tissue
     IHTG, %−0.39*0.08−0.24−0.49**
     HISI0.45*−0.020.270.47**
     Insulin stimulation of glucose Rd, %0.270.230.220.57***
     Insulin suppression of palmitate Ra,† %0.52*0.220.300.56**
     VLDL-TG production rate, µmol/min−0.45*−0.14−0.20−0.40*
     VLDL-apoB100 production rate,† nmol/min−0.44*−0.49*−0.55**−0.49*
     CD36 total mRNA—0.270.58**0.68***
     CD36 protein,‡0.75***0.320.46*0.58**
     VAT, cm3−0.09−0.39*−0.10−0.47*
     FM, %0.43*0.050.47*0.36*
    Skeletal muscle
     VLDL-TG clearance, mL/min0.35*0.38*0.40*−0.16
     FFA Rd, µmol/kg FFM/min0.58**0.45*0.54**−0.32
    • Shown are Spearman r correlations and corresponding P values.

    • ↵Protein expression level in arbitrary units. *P < 0.05.

    • ↵**P < 0.001.

    • ↵***P < 0.0001.

    • ↵†n = 36.

    • ↵‡n = 26 for skeletal muscle.

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Adipose and Muscle Tissue Profile of CD36 Transcripts in Obese Subjects Highlights the Role of CD36 in Fatty Acid Homeostasis and Insulin Resistance
Terri A. Pietka, Timothy Schappe, Caterina Conte, Elisa Fabbrini, Bruce W. Patterson, Samuel Klein, Nada A. Abumrad, Latisha Love-Gregory
Diabetes Care Jul 2014, 37 (7) 1990-1997; DOI: 10.2337/dc13-2835

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Adipose and Muscle Tissue Profile of CD36 Transcripts in Obese Subjects Highlights the Role of CD36 in Fatty Acid Homeostasis and Insulin Resistance
Terri A. Pietka, Timothy Schappe, Caterina Conte, Elisa Fabbrini, Bruce W. Patterson, Samuel Klein, Nada A. Abumrad, Latisha Love-Gregory
Diabetes Care Jul 2014, 37 (7) 1990-1997; DOI: 10.2337/dc13-2835
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