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Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting ß3‐adrenergic receptor/mTORC1 signaling
Author(s) -
Chen Sisi,
Mei Xiaohan,
Yin Amelia,
Yin Hang,
Cui Xiao-Bing,
Chen Shi-You
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701508r
Subject(s) - prdm16 , white adipose tissue , adipose tissue , mtorc1 , biology , brown adipose tissue , endocrinology , medicine , pi3k/akt/mtor pathway , gene expression , protein kinase b , adipose tissue macrophages , stromal vascular fraction , signal transduction , microbiology and biotechnology , gene , genetics
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 ß3‐adrenergic receptor (ß3‐AR) expression and subsequent activation of mammalian target of rapamycin complex (mTORC)‐1. ß3‐AR antagonist SR 59230A and mTORC1 inhibitor rapamycin blocked Rgc32 −/− ‐induced thermogenic gene expression in both iWAT and inter‐scapular BAT. These results indicate that RGC‐32 suppresses adipose tissue thermogenic gene expression through down‐regulation of ß3‐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. FASEB J. 32, 4836–4847 (2018). www.fasebj.org