A hepatic GAbp-AMPK axis links inflammatory signaling to systemic vascular damage

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Veröffentlicht in:	Cell reports 20(2017), 6, Seite 1422-1434; volume:20; number:6; year:2017; extent:13; pages:1422-1434
Personen und Körperschaften:	Niopek, Katharina (VerfasserIn), Sakurai, Minako (VerfasserIn), Feuchter, Yvonne (VerfasserIn), Leuchs, Barbara (VerfasserIn), Niopek, Dominik (VerfasserIn), Brune, Maik (VerfasserIn), Sticht, Carsten (VerfasserIn), Gretz, Norbert (VerfasserIn), Hammes, Hans-Peter (VerfasserIn), Nawroth, Peter Paul (VerfasserIn), Fleming, Thomas (VerfasserIn), Herzig, Stephan (VerfasserIn), Berriel Diaz, Mauricio (VerfasserIn)
Titel:	A hepatic GAbp-AMPK axis links inflammatory signaling to systemic vascular damage/ Katharina Niopek, Bilgen Ekim Üstünel, Susanne Seitz, Minako Sakurai, Annika Zota, Frits Mattijssen, Xiaoyue Wang, Tjeerd Sijmonsma, Yvonne Feuchter, Anna M. Gail, Barbara Leuchs, Dominik Niopek, Oskar Staufer, Maik Brune, Carsten Sticht, Norbert Gretz, Karin Müller-Decker, Hans-Peter Hammes, Peter Nawroth, Thomas Fleming, Michael D. Conkright, Matthias Blüher, Anja Zeigerer, Stephan Herzig, and Mauricio Berriel Diaz
Format:	E-Book-Kapitel
Sprache:	Englisch
veröffentlicht:	August 8, 2017
Gesamtaufnahme:	: Cell reports, 20(2017), 6, Seite 1422-1434 , volume:20
Schlagwörter:	AMPK atherogenesis GAbp liver TNF-α
Quelle:	Verbunddaten SWB Lizenzfreie Online-Ressourcen

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Zusammenfassung:	Increased pro-inflammatory signaling is a hallmark of metabolic dysfunction in obesity and diabetes. Although both inflammatory and energy substrate handling processes represent critical layers of metabolic control, their molecular integration sites remain largely unknown. Here, we identify the heterodimerization interface between the α and β subunits of transcription factor GA-binding protein (GAbp) as a negative target of tumor necrosis factor alpha (TNF-α) signaling. TNF-α prevented GAbpα and β complex formation via reactive oxygen species (ROS), leading to the non-energy-dependent transcriptional inactivation of AMP-activated kinase (AMPK) β1, which was identified as a direct hepatic GAbp target. Impairment of AMPKβ1, in turn, elevated downstream cellular cholesterol biosynthesis, and hepatocyte-specific ablation of GAbpα induced systemic hypercholesterolemia and early macro-vascular lesion formation in mice. As GAbpα and AMPKβ1 levels were also found to correlate in obese human patients, the ROS-GAbp-AMPK pathway may represent a key component of a hepato-vascular axis in diabetic long-term complications.
Beschreibung:	Gesehen am 26.07.2018
Umfang:	13
ISSN:	2211-1247
DOI:	10.1016/j.celrep.2017.07.023