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Obesity-induced nucleosome release predicts poor cardio-metabolic health

O. Lo Re, A. Maugeri, J. Hruskova, J. Jakubik, J. Kucera, J. Bienertova-Vasku, JA. Oben, L. Kubala, A. Dvorakova, M. Ciz, M. Vinciguerra,

. 2019 ; 12 (1) : 2. [pub] 20191231

Language English Country Germany

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20025333

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.

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$a Lo Re, Oriana $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic. Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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$a 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.
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$a Maugeri, Andrea $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic. Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Catania, Italy.
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$a Hruskova, Jana $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic.
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$a Kucera, Jan $u Research Centre for Toxic Compounds in the Environment (RECETOX), Faculty of Science, Masaryk University, Brno, Czech Republic.
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$a Bienertova-Vasku, Julie $u Research Centre for Toxic Compounds in the Environment (RECETOX), Faculty of Science, Masaryk University, Brno, Czech Republic. Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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$a Oben, Jude A $u Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London, UK.
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$a Kubala, Lukas $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic. Institute of Biophysics, Academy of Sciences of the Czech Republic, 61265, Brno, Czech Republic.
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$a Dvorakova, Adela $u Institute of Biophysics, Academy of Sciences of the Czech Republic, 61265, Brno, Czech Republic. Department of Animal Physiology and Immunology, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic.
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$a Ciz, Milan $u Institute of Biophysics, Academy of Sciences of the Czech Republic, 61265, Brno, Czech Republic. Department of Animal Physiology and Immunology, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic.
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$a Vinciguerra, Manlio $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic. manlio.vinciguerra@fnusa.cz. Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London, UK. manlio.vinciguerra@fnusa.cz.
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