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

被引：106

作者：

Shimizu, Noriaki ^{[1
]}

Maruyama, Takako ^{[1
]}

Yoshikawa, Noritada ^{[1
]}

Matsumiya, Ryo ^{[1
]}

Ma, Yanxia ^{[1
]}

Ito, Naoki ^{[2
]}

Tasaka, Yuki ^{[1
]}

Kuribara-Souta, Akiko ^{[1
]}

Miyata, Keishi ^{[3
]}

Oike, Yuichi ^{[3
]}

Berger, Stefan ^{[4
]}

Schuetz, Guenther ^{[4
]}

Takeda, Shin'ichi ^{[2
]}

Tanaka, Hirotoshi ^{[1
,5
]}

机构：

[1] Univ Tokyo, Inst Med Sci, IMSUT Hosp, Dept Rheumatol & Allergy,Minato Ku, Tokyo 1088639, Japan

[2] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mol Therapy, Kodaira, Tokyo 1878502, Japan

[3] Kumamoto Univ, Grad Sch Med Sci, Dept Mol Genet, Chuo Ku, Kumamoto 8608556, Japan

[4] German Canc Res Ctr, Div Mol Biol Cell 1, D-69120 Heidelberg, Germany

[5] Univ Tokyo, Inst Med Sci, IMSUT Hosp, Div Rheumatol,Ctr Antibody & Vaccine,Minato Ku, Tokyo 1088639, Japan

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

GROWTH-FACTOR; 21; ENDOPLASMIC-RETICULUM STRESS; INSULIN-RESISTANCE; SKELETAL-MUSCLE; GLUCOCORTICOID-RECEPTOR; ALANINE AMINOTRANSFERASE; ENERGY-EXPENDITURE; LIPID-METABOLISM; PPAR-ALPHA; FGF21;

D O I：

10.1038/ncomms7693

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 37 条

[1]

Badman MK, 2007, CELL METAB, V5, P426, DOI 10.1016/j.cmet.2007.05.002

[2]

Bertorini Tulio E, 2014, Handb Clin Neurol, V120, P749, DOI 10.1016/B978-0-7020-4087-0.00050-4

[3] Alanine aminotransferase levels and fatty liver in childhood obesity: Associations with insulin resistance, adiponectin, and visceral fat [J].