Journal Article

DKFZ-2017-03538

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling.

Shimizu, N. ; Maruyama, T. ; Yoshikawa, N. ; Matsumiya, R. ; Ma, Y. ; Ito, N. ; Tasaka, Y. ; Kuribara-Souta, A. ; Miyata, K. ; Oike, Y. ; Berger, S.DKFZ* ; Schütz, G.DKFZ* ; Takeda, S. ; Tanaka, H.

2015
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/ncomms7693

Abstract: Skeletal muscle has a pleiotropic role in organismal energy metabolism, for example, by storing protein as an energy source, or by excreting endocrine hormones. Muscle proteolysis is tightly controlled by the hypothalamus-pituitary-adrenal signalling axis via a glucocorticoid-driven transcriptional programme. Here we unravel the physiological significance of this catabolic process using skeletal muscle-specific glucocorticoid receptor (GR) knockout (GRmKO) mice. These mice have increased muscle mass but smaller adipose tissues. Metabolically, GRmKO mice show a drastic shift of energy utilization and storage in muscle, liver and adipose tissues. We demonstrate that the resulting depletion of plasma alanine serves as a cue to increase plasma levels of fibroblast growth factor 21 (FGF21) and activates liver-fat communication, leading to the activation of lipolytic genes in adipose tissues. We propose that this skeletal muscle-liver-fat signalling axis may serve as a target for the development of therapies against various metabolic diseases, including obesity.

Keyword(s): NR3C1 protein, mouse ; Receptors, Glucocorticoid ; fibroblast growth factor 21 ; Fibroblast Growth Factors ; Alanine

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Contributing Institute(s):

1. Helmholtz-Professur Molekularbiologie der Zelle I (A992)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2015

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