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Heidenreich, S.* ; Witte, N.* ; Weber, P.* ; Goehring, I.* ; Tolkachov, A.* ; von Loeffelholz, C.* ; Doecke, S.* ; Bauer, M.* ; Stockmann, M.* ; Pfeiffer, A.F.H.* ; Birkenfeld, A.L. ; Pietzke, M.* ; Kempa, S.* ; Muenzner, M.* ; Schupp, M.*

Retinol saturase coordinates liver metabolism by regulating ChREBP activity.

Nat. Commun. 8:384 (2017)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
The liver integrates multiple metabolic pathways to warrant systemic energy homeostasis. An excessive lipogenic flux due to chronic dietary stimulation contributes to the development of hepatic steatosis, dyslipidemia and hyperglycemia. Here we show that the oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. Liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. Thus, RetSat is a critical regulator of liver metabolism functioning upstream of ChREBP. Pharmacological inhibition of liver RetSat may represent a therapeutic approach for steatosis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Element-binding Protein; Genome-wide Analysis; De-novo Lipogenesis; Large Gene Lists; Response Element; Insulin-resistance; Transcription Factor; Glucose-metabolism; Hepatic Steatosis; Plasma-glucose
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 384 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)