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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)
Publ. Version/Full Text Research data DOI PMC
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Element-binding Protein; Genome-wide Analysis; De-novo Lipogenesis; Large Gene Lists; Response Element; Insulin-resistance; Transcription Factor; Glucose-metabolism; Hepatic Steatosis; Plasma-glucose
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 8, Issue: , Pages: , Article Number: 384 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-012
PubMed ID 28855500
DOI 10.1038/s41467-017-00430-w
WOS ID WOS:000408695100001
Scopus ID 85028563845
Erfassungsdatum 2017-09-22
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