Lo Re, O;
Maugeri, A;
Hruskova, J;
Jakubik, J;
Kucera, J;
Bienertova-Vasku, J;
Oben, JA;
... Vinciguerra, M; + view all
(2019)
Obesity-induced nucleosome release predicts poor cardio-metabolic health.
Clinical Epigenetics
, 12
(1)
, Article 2. 10.1186/s13148-019-0797-8.
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Abstract
Objective: While circulating nucleosome levels are high in obese mouse models, it is unknown where these nucleosomes originate from and whether they are a marker of cardio-metabolic health in humans. Here, we aimed to determine whether an association exists between circulating nucleosomes and the risk of developing obesity, metabolic syndrome (MetS) and/or a dysfunctional cardiovascular performance. / Methods: We randomly selected 120 participants of the Kardiovize Brno 2030 study across three BMI strata: BMI 18–25, 25–30, and > 30. We assessed the association between circulating nucleosome levels and the risk of obesity, MetS, and poor cardiovascular health. We then cultured human neutrophils, adipocytes, and hepatoma cells to study nucleosome origins in a fat-rich environment. Results: Circulating nucleosome levels positively correlated with BMI (R = 0.602, p < 0.05), fatty liver index (R = 0.622, p < 0.05), left ventricular mass (R = 0.457, p < 0.05), and associated with MetS (p < 0.001) and poor cardiovascular health (p < 0.001). Incubating neutrophils with 1–10 μM free fatty acids triggered nucleosome production without concomitant cell death. Nucleosomes were not produced during pre-adipocyte differentiation or upon incubation of hepatic cells with palmitic acid. / Conclusions: Neutrophils are a bona fide source of circulating nucleosomes in an obesogenic environment and in overweight/obese patients. High nucleosome levels are associated with MetS and cardiovascular performance, and might represent novel candidate biomarkers for cardio-metabolic health.
| Type: | Article |
|---|---|
| Title: | Obesity-induced nucleosome release predicts poor cardio-metabolic health |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13148-019-0797-8 |
| Publisher version: | http://dx.doi.org/10.1186/s13148-019-0797-8 |
| Language: | English |
| Additional information: | © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Liquid biopsy, Nucleosome, Epigenetics, Metabolic health, Cardiovascular disease, CARDIOVASCULAR-DISEASE, CIRCULATING NUCLEOSOMES, NEUTROPHIL ACTIVATION, AMERICAN SOCIETY, RISK, ECHOCARDIOGRAPHY, RECOMMENDATIONS, INFLAMMATION, ASSOCIATION, CHROMATIN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10117446 |
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