Cell-Free DNA as an Obesity Biomarker

Zovico, Paulo Vinicios Camuzi; Neto, Victor Hugo Gasparini; Venâncio, Fernanda A; Miguel, Gustavo Peixoto Soares; Pedrosa, Rogério Graça; Haraguchi, Fabiano Kenji; Baraúna, Valério Garrone

doi:10.33549/physiolres.934242

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…The major outcome is that ecDNA is associated with the overall cardiometabolic risk score rather than with obesity alone. This is in line with the observation that ecDNA correlates with body fat and inflammation but not with BMI (55). Similarly, bariatric surgery as the most effective treatment of obesity leads to a decrease of ecDNA but only in diabetic subjects (56).…”

Section: Discussionsupporting

confidence: 88%

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents

Celec

Janovičová

Gurecká

et al. 2021

Physiological Genomics

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Obesity is associated with chronic low-grade inflammation that eventually leads to metabolic complications. Extracellular DNA (ecDNA) is a damage-associated molecular pattern. Extracellular mitochondrial DNA can activate innate immunity. We hypothesized that ecDNA, especially of mitochondrial origin could be associated with components of the metabolic syndrome in young healthy probands. In a cross-sectional study healthy adolescents (n=1249) provided blood samples. Anthropometric data, blood pressure and blood counts were assessed. In addition, biochemical analysis of sera or plasma was conducted including the quantification of advanced oxidation protein products (AOPP) as a marker of oxidative stress induced by neutrophil or monocyte activation. Plasma ecDNA was isolated and measured using fluorometry. Nuclear and mitochondrial DNA were quantified using real time PCR. Males had higher total plasma ecDNA (15 (11-21) vs 11 (8-17) ng/ml; median (IQR)), nuclear (1760 (956-3273) vs 1153 (600-2292) GE/ml) and mitochondrial DNA (37181 (14836-90896) vs 30089 (12587-72286) GE/ml). EcDNA correlated positively with the continuous metabolic syndrome score (r= 0.158 for males and r= 0.134 for females). Stronger correlations were found between ecDNA of mitochondrial origin and AOPP (r= 0.202 and 0.186 for males and females respectively). Multivariate regression analysis revealed associations of nuclear DNA with leukocyte and erythrocyte counts. The results of this study on healthy adolescents show that circulating ecDNA is associated with the risk of metabolic syndrome, not with obesity per se. The association between mitochondrial ecDNA and AOPP requires further attention as it supports a potential role of mitochondria-induced sterile inflammation in the pathogenesis of the metabolic syndrome.

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Section: Discussionsupporting

confidence: 88%

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents

Celec

Janovičová

Gurecká

et al. 2021

Physiological Genomics

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“…Indeed, the above-mentioned related studies have had a higher male percentage: ~41% (9) and ~37% [ 10 , 11 ] vs. ~31% male in our study. Interestingly, similar to our study, the decrease in body weight and fat percentage did not result in changes in cf-DNA levels six months after bariatric surgery [ 23 ]. Additionally, we need to mention that some data for 3 M and 6 M post-surgery were missing for different patients at different times, partially due to the COVID-19 pandemic-related missed visits ( Table 1 ).…”

Section: Discussionsupporting

confidence: 89%

Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients

Yuzefovych,

Pastukh,

Mulekar

et al. 2023

Biomedicines

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While improvement of mitochondrial function after bariatric surgery has been demonstrated, there is limited evidence about the effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA) and intracellular mtDNA abundance. Plasma and peripheral blood mononuclear (PBM) cells were isolated from healthy controls (HC) and bariatric surgery patients before surgery and 2 weeks, 3 months, and 6 months after surgery. At baseline, the plasma level of short cf-mtDNA (ND6, ~100 bp) fragments was significantly higher in obese patients compared to HC. But there was no significant variation in mean ND6 values post-surgery. A significant positive correlation was observed between preop plasma ND6 levels and HgbA1c, ND6 and HOMA-IR 2 weeks post-surgery, and mtDNA content 6 months post-surgery. Interestingly, plasma from both HC and obese groups at all time points post-surgery contains long (~8 kb) cf-mtDNA fragments, suggesting the presence of near-intact and/or whole mitochondrial genomes. No significant variation was observed in mtDNA content post-surgery compared to baseline data in both PBM and skeletal muscle samples. Overall, bariatric surgery improved insulin sensitivity and other metabolic parameters without significant changes in plasma short cf-mtDNA levels or cellular mtDNA content. Our study provides novel insights about possible molecular mechanisms underlying the metabolic effects of bariatric surgery and suggests the development of new generalized approaches to characterize cf-mtDNA.

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“…The most common size of cfDNA found is~166 bp and consists of a histone-complexed DNA, called nucleosome [136,137]. This is the main cfDNA size found in plasma from all kinds of health or disease subjects [29,[138][139][140]. In healthy individuals, the cfDNA size has been described to vary mainly between 70 to 200 bp [141][142][143].…”

Section: Cfdna Integritymentioning

confidence: 99%

Properties and Application of Cell-Free DNA as a Clinical Biomarker

Miranda

Baraúna

Santos

et al. 2021

IJMS

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Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized the definition of a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. A biomarker has clinical relevance when it presents precision, standardization and reproducibility, suitability to the patient, straightforward interpretation by clinicians, and high sensitivity and/or specificity by the parameter it proposes to identify. Thus, serum biomarkers should have advantages related to the simplicity of the procedures and to the fact that venous blood collection is commonplace in clinical practice. We described the potentiality of cfDNA as a general clinical biomarker and focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. An increasing number of studies demonstrate the potential use of cfDNA as a noninvasive biomarker to determine physiologic and pathologic conditions. However, although still scarce, increasing evidence has been reported regarding using cfDNA in cardiovascular diseases. Here, we have reviewed the history of cfDNA, its source, molecular features, and release mechanism. We also show recent studies that have investigated cfDNA as a possible marker of endothelial damage in clinical settings. In the cardiovascular system, the studies are quite new, and although interesting, stronger evidence is still needed. However, some drawbacks in cfDNA methodologies should be overcome before its recommendation as a biomarker in the clinical setting.

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Cell-Free DNA as an Obesity Biomarker

Cited by 11 publications

References 19 publications

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents

Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients

Properties and Application of Cell-Free DNA as a Clinical Biomarker

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