Autophagy inhibition prevents glucocorticoid-increased adiposity via suppressing BAT whitening

被引：60

作者：

Deng, Jiali ^{[1
]}

Guo, Yajie ^{[1
]}

Yuan, Feixiang ^{[1
]}

Chen, Shanghai ^{[1
]}

Yin, Hanrui ^{[1
]}

Jiang, Xiaoxue ^{[1
]}

Jiao, Fuxin ^{[1
]}

Wang, Fenfen ^{[1
]}

Ji, Hongbin ^{[2
]}

Hu, Guohong ^{[3
,4
]}

Ying, Hao ^{[1
]}

Chen, Yan ^{[1
]}

Zhai, Qiwei ^{[1
]}

Xiao, Fei ^{[1
]}

Guo, Feifan ^{[1
]}

机构：

[1] Univ Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci,Chinese Acad Sci, Shanghai, Peoples R China

[2] Univ Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci,Chinese Acad Sci, Shanghai, Peoples R China

[3] Chinese Acad Sci, Key Lab Stem Cell Biol, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China

来源：

AUTOPHAGY | 2020年 / 16卷 / 03期

关键词：

ATG7; autophagy; BAT whitening; BTG1; glucocorticoid; AMELIORATES LIVER STEATOSIS; BROWN FAT; OXIDATIVE STRESS; BTG1; RECEPTOR; MICE; DIFFERENTIATION; THERMOGENESIS; ADIPOGENESIS; ACTIVATION;

D O I：

10.1080/15548627.2019.1628537

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The mechanisms underlying glucocorticoid (GC)-increased adiposity are poorly understood. Brown adipose tissue (BAT) acquires white adipose tissue (WAT) cell features defined as BAT whitening under certain circumstances. The aim of our current study was to investigate the possibility and mechanisms of GC-induced BAT whitening. Here, we showed that one-week dexamethasone (Dex) treatment induced BAT whitening, characterized by lipid droplet accumulation, in vitro and in vivo. Furthermore, autophagy and ATG7 (autophagy related 7) expression was induced in BAT by Dex, and treatment with the autophagy inhibitor chloroquine or adenovirus-mediated ATG7 knockdown prevented Dex-induced BAT whitening and fat mass gain. Moreover, Dex-increased ATG7 expression and autophagy was mediated by enhanced expression of BTG1 (B cell translocation gene 1, anti-proliferative) that stimulated activity of CREB1 (cAMP response element binding protein 1). The importance of BTG1 in this regulation was further demonstrated by the observed BAT whitening in adipocyte-specific BTG1-overexpressing mice and the attenuated Dex-induced BAT whitening and fat mass gain in mice with BTG1 knockdown in BAT. Taken together, we showed that Dex induces a significant whitening of BAT via BTG1- and ATG7-dependent autophagy, which might contribute to Dex-increased adiposity. These results provide new insights into the mechanisms underlying GC-increased adiposity and possible strategy for preventing GC-induced side effects via the combined use of an autophagy inhibitor.

引用

页码：451 / 465

页数：15

共 51 条

[21] The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase [J].