PuSH - Publikationsserver des Helmholtz Zentrums München: Tick-tock hedgehog-mutual crosstalk with liver circadian clock promotes liver steatosis.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Marbach-Breitrück, E.* ; Matz-Soja, M.* ; Abraham, U.* ; Schmidt-Heck, W.* ; Sales, S.* ; Rennert, C.* ; Kern, M.* ; Aleithe, S.* ; Spormann, L.* ; Thiel, C.* ; Gerlini, R. ; Arnold, K.* ; Klöting, N.* ; Guthke, R.* ; Rozman, D.* ; Teperino, R. ; Shevchenko, A.* ; Krämer, A.* ; Gebhardt, R.*

Tick-tock hedgehog-mutual crosstalk with liver circadian clock promotes liver steatosis.

J. Hepatol. 70, 1192-1202 (2019)

Postprint

Forschungsdaten

DOI

PMC

	Open Access Green

Abstract
Metriken
Zusatzinfos

Background & Aims: The mammalian circadian clock controls various aspects of liver metabolism and integrates nutritional signals. Recently, we described Hedgehog (Hh) signaling as a novel regulator of liver lipid metabolism. Herein, we investigated crosstalk between hepatic Hh signaling and circadian rhythm.Methods: Diurnal rhythms of Hh signaling were investigated in liver and hepatocytes from mice with ablation of Smoothened (SAC-KO) and crossbreeds with PER2::LUC reporter mice. By using genome-wide screening, qPCR, immunostaining, ELISA and RNAi experiments in vitro we identified relevant transcriptional regulatory steps. Shotgun lipidomics and metabolic cages were used for analysis of metabolic alterations and behavior.Results: Hh signaling showed diurnal oscillations in liver and hepatocytes in vitro. Correspondingly, the level of Indian Hh, oscillated in serum. Depletion of the clock gene Bmal1 in hepatocytes resulted in significant alterations in the expression of Hh genes. Conversely, SAC-KO mice showed altered expression of clock genes, confirmed by RNAi against Gli1 and Gli3. Genome-wide screening revealed that SAC-KO hepatocytes showed time-dependent alterations in various genes, particularly those associated with lipid metabolism. The clock/hedgehog module further plays a role in rhythmicity of steatosis, and in the response of the liver to a high-fat diet or to differently timed starvation.Conclusions: For the first time, Hh signaling in hepatocytes was found to be time-of-day dependent and to feed back on the circadian clock. Our findings suggest an integrative role of Hh signaling, mediated mainly by GLI factors, in maintaining homeostasis of hepatic lipid metabolism by balancing the circadian clock.Lay summary: The results of our investigation show for the first time that the Hh signaling in hepatocytes is time-of-day dependent, leading to differences not only in transcript levels but also in the amount of Hh ligands in peripheral blood. Conversely, Hh signaling is able to feed back to the circadian clock. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

18.946

3.607