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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 |
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| Personen und Körperschaften: | , , , , , , , , , , , , |
| 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: | |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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| 520 | |a 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. | ||
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| author | Niopek, Katharina, Sakurai, Minako, Feuchter, Yvonne, Leuchs, Barbara, Niopek, Dominik, Brune, Maik, Sticht, Carsten, Gretz, Norbert, Hammes, Hans-Peter, Nawroth, Peter Paul, Fleming, Thomas, Herzig, Stephan, Berriel Diaz, Mauricio |
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| contents | 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. |
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| spelling | Niopek, Katharina VerfasserIn (DE-588)1147589313 (DE-627)100633808X (DE-576)495879312 aut, 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, August 8, 2017, 13, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 26.07.2018, 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., AMPK, atherogenesis, GAbp, liver, TNF-α, Sakurai, Minako VerfasserIn (DE-588)1190045109 (DE-627)1668725517 aut, Feuchter, Yvonne VerfasserIn (DE-588)113914426X (DE-627)897309952 (DE-576)492956898 aut, Leuchs, Barbara VerfasserIn (DE-588)1190055112 (DE-627)1668742330 aut, Niopek, Dominik VerfasserIn (DE-588)107173685X (DE-627)826298109 (DE-576)433282479 aut, Brune, Maik 1974- VerfasserIn (DE-588)130611883 (DE-627)504641948 (DE-576)298297930 aut, Sticht, Carsten 1972- VerfasserIn (DE-588)1020115718 (DE-627)691110077 (DE-576)250042177 aut, Gretz, Norbert 1954- VerfasserIn (DE-588)1020104589 (DE-627)691105154 (DE-576)359544843 aut, Hammes, Hans-Peter 1955- VerfasserIn (DE-588)102028353X (DE-627)691169772 (DE-576)360007252 aut, Nawroth, Peter Paul 1954- VerfasserIn (DE-588)1020504897 (DE-627)69123941X (DE-576)360517692 aut, Fleming, Thomas 1982- VerfasserIn (DE-588)1034445294 (DE-627)745607365 (DE-576)382066804 aut, Herzig, Stephan 1969- VerfasserIn (DE-588)12146623X (DE-627)705470857 (DE-576)292725949 aut, Berriel Diaz, Mauricio 1971- VerfasserIn (DE-588)1124103996 (DE-627)877827648 (DE-576)482304693 aut, Enthalten in Cell reports Maryland Heights, MO : Cell Press, 2012 20(2017), 6, Seite 1422-1434 Online-Ressource (DE-627)684964562 (DE-600)2649101-1 (DE-576)358411572 2211-1247 nnns, volume:20 year:2017 number:6 pages:1422-1434 extent:13, http://dx.doi.org/10.1016/j.celrep.2017.07.023 Verlag Resolving-System kostenfrei Volltext, http://www.sciencedirect.com/science/article/pii/S2211124717309890 Verlag kostenfrei Volltext, http://dx.doi.org/10.1016/j.celrep.2017.07.023 LFER, LFER epn:3020647436 2018-08-13T00:00:00Z |
| spellingShingle | Niopek, Katharina, Sakurai, Minako, Feuchter, Yvonne, Leuchs, Barbara, Niopek, Dominik, Brune, Maik, Sticht, Carsten, Gretz, Norbert, Hammes, Hans-Peter, Nawroth, Peter Paul, Fleming, Thomas, Herzig, Stephan, Berriel Diaz, Mauricio, A hepatic GAbp-AMPK axis links inflammatory signaling to systemic vascular damage, 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., AMPK, atherogenesis, GAbp, liver, TNF-α |
| swb_id_str | 507965388 |
| title | A hepatic GAbp-AMPK axis links inflammatory signaling to systemic vascular damage |
| title_auth | A hepatic GAbp-AMPK axis links inflammatory signaling to systemic vascular damage |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_in_hierarchy | 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, |
| title_short | A hepatic GAbp-AMPK axis links inflammatory signaling to systemic vascular damage |
| title_sort | a hepatic gabp-ampk axis links inflammatory signaling to systemic vascular damage |
| title_unstemmed | A hepatic GAbp-AMPK axis links inflammatory signaling to systemic vascular damage |
| topic | AMPK, atherogenesis, GAbp, liver, TNF-α |
| topic_facet | AMPK, atherogenesis, GAbp, liver, TNF-α |
| url | http://dx.doi.org/10.1016/j.celrep.2017.07.023, http://www.sciencedirect.com/science/article/pii/S2211124717309890 |
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