Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting β3-adrenergic receptor/mTORC1 signaling

Our previous studies have shown that response gene to complement (RGC)-32 deficiency (Rgc32 ) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues. However, the underlying mechanisms by which RGC-32 regulates thermogenic gene expression remain to be de...

Full description

Saved in:
Bibliographic Details
Published in:The FASEB journal 2018-09, Vol.32 (9), p.4836-4847
Main Authors: Chen, Sisi, Mei, Xiaohan, Yin, Amelia, Yin, Hang, Cui, Xiao-Bing, Chen, Shi-You
Format: Article
Language:English
Subjects:
Adipose Tissue - metabolism
Adipose Tissue, Brown - metabolism
Adipose Tissue, White - metabolism
Animals
Cell Differentiation - genetics
Complement System Proteins - metabolism
Mechanistic Target of Rapamycin Complex 1 - metabolism
Mice, Knockout
Nuclear Proteins - deficiency
Nuclear Proteins - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Receptors, Adrenergic, beta-3 - metabolism
Signal Transduction - genetics
Thermogenesis - genetics
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Our previous studies have shown that response gene to complement (RGC)-32 deficiency (Rgc32 ) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues. However, the underlying mechanisms by which RGC-32 regulates thermogenic gene expression remain to be determined. In the present study, RGC-32 expression in white adipose tissue (WAT) was suppressed during cold exposure-induced WAT browning. Rgc32 significantly increased thermogenic gene expression in the differentiated stromal vascular fraction (SVF) of inguinal (i)WAT and interscapular brown adipose tissue (BAT). Rgc32 and cold exposure regulated a common set of genes in iWAT, as shown by RNA sequencing data. Pathway enrichment analyses showed that Rgc32 down-regulated PI3K/Akt signaling-related genes. Akt phosphorylation was also consistently decreased in Rgc32 iWAT, which led to an increase in β3-adrenergic receptor (β3-AR) expression and subsequent activation of mammalian target of rapamycin complex (mTORC)-1. β3-AR antagonist SR 59230A and mTORC1 inhibitor rapamycin blocked Rgc32 -induced thermogenic gene expression in both iWAT and interscapular BAT. These results indicate that RGC-32 suppresses adipose tissue thermogenic gene expression through down-regulation of β3-AR expression and mTORC1 activity via a PI3K/Akt-dependent mechanism.-Chen, S., Mei, X., Yin, A., Yin, H., Cui, X.-B., Chen, S.-Y. Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting β3-adrenergic receptor/mTORC1 signaling.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201701508R