Monocyte heterogeneity in obesity and subclinical atherosclerosis
ABSTRACT AIMS: Monocytes and monocyte-derived macrophages have been recognised as the cellular hallmark of atherosclerosis decades ago. Recently, they have also been shown to play a pivotal role in obesity. Monocytes display immunophenotypic heterogeneity with functionally distinct subpopulations. We initiated the I LIKE HOMe study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis. METHODS AND RESULTS: We assessed carotid intima media thickness (IMT), body mass index (BMI), and other cardiovascular risk factors in 622 healthy volunteers. Using flow-cytometry, we differentiated monocytes into CD14(++)CD16(-) and CD16(+) cells, which we further subdivided into CD14(++)CD16(+) and CD14((+))CD16(+) cells. Body mass index was significantly correlated with carotid IMT. High CD16(+) monocyte counts were significantly associated with both higher BMI and increased carotid IMT. Adjustment for CD16(+) monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16(+) monocyte numbers in obesity may partly explain the association between obesity and IMT. Conclusion: Our results reveal a significant univariate association between CD16(+) monocytes and both obesity and subclinical atherosclerosis in low-risk individuals. They are in line with recent observations that CD16(+) monocytes show high endothelial affinity and a potent capacity to invade vascular lesions and to transform into pro-inflammatory cytokine producing macrophages.
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ABSTRACT: Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity.12/2012; 2012:205027. DOI:10.6064/2012/205027
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ABSTRACT: This paper presents a weak magnetic field measurement system using micro-fluxgate sensors and a sensor signal processing technique using the sigma-delta modulation in the negative feedback loop. The feedback of low-pass filtered bitstream output of a sigma-delta modulator to the magnetic field improves system linearity, hysteresis and stability. The third-order noise shaping can be obtained in the digital output bit-stream by the use of an integrator in the loop. Earth's magnetic field is successfully measured. The non-linearity error is less then 0.4 % in the range of ± 100 μT.Instrumentation and Measurement Technology Conference, 2002. IMTC/2002. Proceedings of the 19th IEEE; 02/2002
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ABSTRACT: Excessive weight gain increases systemic inflammation resulting in increased disease risk. Toll-like receptor 4 (TLR4) reportedly mediates increases in inflammation; however, its role has not been fully evaluated. Objective. The purpose of this study was to determine the longitudinal effect of diet-induced weight gain on blood monocyte concentration and cell-surface TLR4 expression. Research Methods & Procedures. Male CD-1 mice were randomly assigned to high-fat (HF, n = 12) or low-fat (LF, n = 13) groups. Non-lethal, saphenous vein blood samples were collected at 0, 4, 8 and 12 weeks of treatment. Three-color flow cytometry was used to measure monocyte (CD11b+/CD14+) concentration and TLR4 cells-surface expression. Data were analyzed with a repeated measures ANOVA; significance was set at P<0.05. Results. Body weight at week 12 was 21% greater in HF than LF (P<0.05). At week 12 HF had 155% more monocytes (P<0.05) with 24% less TLR4; Monocyte concentration and body weight at week 12 was negatively correlated with TLR4 gMFI (P<0.05). Conclusions. The observed effects of high-fat feeding on blood monocytes are consistent with a phenotype, which may be associated with premature morbidity. The observed monocyte responses may be associated with immune dysfunction and diminished response to infection.