A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling
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...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
1 April 2015
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| In: |
Nature Communications
Year: 2015, Volume: 6 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms7693 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncomms7693 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncomms7693 
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| Author Notes: | Noriaki Shimizu, Takako Maruyama, Noritada Yoshikawa, Ryo Matsumiya, Yanxia Ma, Naoki Ito, Yuki Tasaka, Akiko Kuribara-Souta, Keishi Miyata, Yuichi Oike, Stefan Berger, Günther Schütz, Shin’ichi Takeda & Hirotoshi Tanaka |
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| 520 | |a 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. | ||
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