Publication details

Obesity-induced nucleosome release predicts poor cardio-metabolic health

Authors

LO RE Oriana MAUGERI Andrea HRUŠKOVÁ Jana JAKUBÍK Juraj KUČERA Jan DOBROVOLNÁ Julie OBEN Jude A. KUBALA Lukas DVOŘÁKOVÁ Adéla ČÍŽ Milan VINCIGUERRA Manlio

Year of publication 2019
Type Article in Periodical
Magazine / Source CLINICAL EPIGENETICS
MU Faculty or unit

Faculty of Medicine

Citation
Web http://dx.doi.org/10.1186/s13148-019-0797-8
Doi http://dx.doi.org/10.1186/s13148-019-0797-8
Keywords Liquid biopsy; Nucleosome; Epigenetics; Metabolic health; Cardiovascular disease
Description 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 mu M 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.
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