Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice

Zidek, L.M.; Ackermann, T.; Hartleben, G.; Eichwald, S.; Kortman, G.; Kiehntopf, M.; Leutz, A.; Sonenberg, N.; Wang, Z.Q.; von Maltzahn, J.; Müller, C.; Calkhoven, C.F.

Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice

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Item Type:	Article
Title:	Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice
Creators Name:	Zidek, L.M., Ackermann, T., Hartleben, G., Eichwald, S., Kortman, G., Kiehntopf, M., Leutz, A., Sonenberg, N., Wang, Z.Q., von Maltzahn, J., Müller, C. and Calkhoven, C.F.
Abstract:	The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of physiological adaptations in response to changes in nutrient supply. Major downstream targets of mTORC1 signalling are the mRNA translation regulators p70 ribosomal protein S6 kinase 1 (S6K1p70) and the 4E-binding proteins (4E-BPs). However, little is known about vertebrate mRNAs that are specifically controlled by mTORC1 signalling and are engaged in regulating mTORC1-associated physiology. Here, we show that translation of the CCAAT/enhancer binding protein beta (C/EBP{beta}) mRNA into the C/EBP{beta}-LIP isoform is suppressed in response to mTORC1 inhibition either through pharmacological treatment or through calorie restriction. Our data indicate that the function of 4E-BPs is required for suppression of LIP. Intriguingly, mice lacking the cis-regulatory upstream open reading frame (uORF) in the C/EBP{beta}-mRNA, which is required for mTORC1-stimulated translation into C/EBP{beta}-LIP, display an improved metabolic phenotype with features also found under calorie restriction. Thus, our data suggest that translational adjustment of C/EBP{beta}-isoform expression is one of the key processes that direct metabolic adaptation in response to changes in mTORC1 activity.
Keywords:	C/EBP{beta}, Calorie Restriction, Metabolism, mTORC1, Translation, Animals, Mice
Source:	EMBO Reports
ISSN:	1469-221X
Publisher:	EMBO Press / Wiley
Volume:	16
Number:	08
Page Range:	1022-1036
Date:	August 2015
Official Publication:	https://doi.org/10.15252/embr.201439837
PubMed:	View item in PubMed

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