Dataset Information

The origin of circulating CD36 in type 2 diabetes.

ABSTRACT:

Objective

Elevated plasma levels of the fatty acid transporter, CD36, have been shown to constitute a novel biomarker for type 2 diabetes mellitus (T2DM). We recently reported such circulating CD36 to be entirely associated with cellular microparticles (MPs) and aim here to determine the absolute levels and cellular origin(s) of these CD36+MPs in persons with T2DM.

Design

An ex vivo case-control study was conducted using plasma samples from 33 obese individuals with T2DM (body mass index (BMI)=39.9±6.4 kg m(-2); age=57±9 years; 18 male:15 female) and age- and gender-matched lean and obese non-T2DM controls (BMI=23.6±1.8 kg m(-2) and 33.5±5.9 kg m(-2), respectively). Flow cytometry was used to analyse surface expression of CD36 together with tissue-specific markers: CD41, CD235a, CD14, CD105 and phosphatidyl serine on plasma MPs. An enzyme-linked immunosorbent assay was used to quantify absolute CD36 protein concentrations.

Results

CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A(1c). By contrast, the main source of CD36+MPs in non-T2DM individuals was endothelial cells (CD105+=40.9±8.3% and 33.9±8.3% for lean and obese controls, respectively). Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml(-1) and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021). Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).

Conclusions

Both the levels and cellular profile of CD36+MPs differ in T2DM compared with controls, suggesting that these specific vesicles could represent distinct biological vectors contributing to the pathology of the disease.

SUBMITTER: Alkhatatbeh MJ

PROVIDER: S-EPMC3584987 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Bariatric surgery is a widely adopted treatment for obesity and its secondary complications. In the past decade, microvesicles (MVs) and CD36 have increasingly been considered as possible biomarkers for obesity, the metabolic syndrome (MetSy), type 2 diabetes mellitus (T2DM). Thus, the purpose of this study was to investigate how weight loss resulting from bariatric surgery affects levels of specific MV phenotypes and their expression of CD36 scavenger receptor. Additionally, we hypothesised that subjects with MetSy had higher baseline concentrations of investigated MV phenotypes. Methods:Twenty individuals undergoing Roux-en-Y gastric bypass surgery were evaluated before and 3 months after surgery. MVs were characterised by flow cytometry at both time points and defined as lactadherin-binding particles within a 100-1000 nm size gate. MVs of monocyte (CD14) and endothelial (CD62E) origin were defined by cell-specific markers, and their expression of CD36 was investigated. Results:Following bariatric surgery, subjects incurred an average BMI reduction (delta) of -?8.4?±?1.4 (p?<?0.0001). Significant reductions were observed for the total MVs (-?66.55%, p?=?0.0017) and MVs of monocyte (-?36.11%, p?=?0.0056) and endothelial (-?40.10%, p?=?0.0007) origins. Although the bulk of CD36-bearing MVs were unaltered, significant reductions were observed for CD36-bearing MVs of monocyte (-?60.04%, p?=?0.0192) and endothelial (-?54.93%, p?=?0.04) origin. No differences in levels of MVs were identified between subjects who presented with MetSy at baseline (n?=?13) and those that did not (n?=?7). Conclusion:Bariatric surgery resulted in significantly altered levels of CD36-bearing MVs of monocyte and endothelial origin. This likely reflects improvements in ectopic fat distribution, plasma lipid profile, low-grade inflammation, and oxidative stress following weight loss. Conversely, however, the presence of MetSy at baseline had no impact on MV phenotypes.