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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: Shimizu, Noriaki (Author) , Maruyama, Takako (Author) , Yoshikawa, Noritada (Author) , Matsumiya, Ryo (Author) , Ma, Yanxia (Author) , Ito, Naoki (Author) , Tasaka, Yuki (Author) , Kuribara-Souta, Akiko (Author) , Miyata, Keishi (Author) , Oike, Yuichi (Author) , Berger, Stefan (Author) , Schütz, Günther (Author) , Takeda, Shin’ichi (Author) , Tanaka, Hirotoshi (Author)
Format: Article (Journal)
Language:English
Published: 1 April 2015
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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Summary: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.
Item Description:Gesehen am 17.06.2020
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/ncomms7693

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