TY  - JOUR
A1  - Speckmann, Bodo
A1  - Schulz, Sarah
A1  - Hiller, Franziska
A1  - Hesse, Deike
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Geisel, Juergen
A1  - Obeid, Rima
A1  - Grune, Tilman
A1  - Kipp, Anna Patricia
T1  - Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice
JF  - The journal of nutritional biochemistry
N2  - The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms. (C) 2017 The Authors. Published by Elsevier Inc.
KW  - Selenium
KW  - DNA methylation
KW  - Liver
KW  - Lipogenesis
KW  - Srebf1
Y1  - 2017
U6  - https://doi.org/10.1016/j.jnutbio.2017.07.002
SN  - 0955-2863
SN  - 1873-4847
VL  - 48
SP  - 112
EP  - 119
PB  - Elsevier
CY  - New York
ER  - 
TY  - GEN
A1  - Castro, José Pedro
A1  - Grune, Tilman
A1  - Speckmann, Bodo
T1  - The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction
N2  - White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 339 
KW  - adipogenesis
KW  - adipose tissue dysregulation
KW  - antioxidants
KW  - metabolic disorders
KW  - oxidative stress
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-398039
ER  -