A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling
Year: 2015
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms7693
Authors: 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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: 骨格筋幹細胞を主点とした骨格筋を含む多臓器ネットワークの解明, Elucidation of the mechanisms of skeletal muscle hypertrophy by intracellular calcium concentration., 凍結破砕技術を利用した個体組織におけるタンパク質―DNA間相互作用解析系の開発, Intervention in fuel choice system for treatment of obesity, Study on homeostatic regulation by glucocorticoid, Identification of novel molecules that improve the transplantation efficiency of muscle stem cells based on their intracellular metabolic state, Mechanism of transcriptional regulation via skeletal muscle glucocorticoid receptor, Development of the molecular basis of novel therapeutic strategy for connective tissue disease-associated pulmonary hypertension
OpenAlex ID: W2123453078