[HTML][HTML] A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling

N Shimizu, T Maruyama, N Yoshikawa… - Nature …, 2015 - nature.com
N Shimizu, T Maruyama, N Yoshikawa, R Matsumiya, Y Ma, N Ito, Y Tasaka…
Nature communications, 2015nature.com
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 …
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.
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