PuSH - Publikationsserver des Helmholtz Zentrums München

Niopek, K.* ; Berriel Diaz, M. ; Nawroth, P.P.* ; Herzig, S.

Mind the Ga(b)p! – a novel hepatic gatekeeper at the switch point of metabolic homeostasis and diabetic late complications controlled by reactive metabolites.

Diabetol. Stoffwechs. 10:P62 (2015)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Introduction: Type 1 and type 2 diabetes and diabetic late complications are often associated with states of chronic inflammation characterized by increased amounts of circulating reactive metabolites and proinflammatory cytokines, such as Tumor necrosis factor-alpha (TNF-α), which affect metabolic tissues by impairing physiologic hormone and nutrient signaling. So far, the molecular response to cytokine signaling in metabolic tissues, including the liver, is only marginally understood.   Results: In a screen to identify transcriptional regulators responsive to inflammatory signaling we found that the activity of the transcription factor GA-binding protein alpha (GAbpα) was reduced in response to TNF-α treatment. Our work identifies GAbp as a novel target of proinflammatory signaling in the liver and furthermore demonstrates that the TNF-α-dependent reduction in activity of the transcription factor is caused by redox-sensitive dissociation of the two subunits GAbpα and GAbpβ. Intriguingly, hepatocyte-specific ablation of GAbp activity proved to be severely atherogenic in LDLRko mice, due to perturbed lipid homeostasis.   Conclusions: As TNF-α and reactive metabolites, including ROS are characteristically increased in metabolic disorders, the TNF-α-dependent ROS-mediated repression of GAbp activity provides a molecular link between inflammation and diabetic derailment. We will further investigate the role of this exceptional regulatory mechanism for diabetic late complications associated with increased proinflammatory signaling, oxidative stress and reactive metabolites. We believe that our novel insights into the interplay of inflammation, ROS and metabolic disorders will provide a new toehold for potential innovative treatment options.   Achnowledgements: Supported by the SFB1118-Reactive metabolites as cause for diabetic complications to S.H. and P.N..
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Meeting abstract
Korrespondenzautor
ISSN (print) / ISBN 1861-9002
e-ISSN 1861-9010
Zeitschrift Diabetologie und Stoffwechsel
Quellenangaben Band: 10, Heft: , Seiten: , Artikelnummer: P62 Supplement: ,
Verlag Thieme
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)