CREG1 administration stimulates BAT thermogenesis and improves diet-induced obesity in mice

被引:6
作者
Kusudo, Tatsuya [1 ,2 ]
Okada, Tadashi [1 ,3 ,4 ]
Hashimoto, Michihiro [1 ,5 ]
Takeuchi, Tamaki [1 ]
Endo, Yuki [1 ]
Niwa, Ayumi [1 ,6 ]
Yamashita, Hitoshi [1 ]
机构
[1] Chubu Univ, Coll Life & Hlth Sci, Dept Biomed Sci, Kasugai, Aichi 4878501, Japan
[2] Tezukayama Gakuin Univ, Fac Human Sci, Sakai, Osaka 5900113, Japan
[3] Tokiwa Fdn, Res Inst Innovat Med RIIM, 57 Kaminodai, Iwaki, Fukushima 9728322, Japan
[4] Iryo Sosei Univ, Ctr Reg Cooperat, 5-5-1 Lino, Iwaki, Fukushima 9708551, Japan
[5] Asahikawa Med Univ, Div Adv Med Sci, 1-1-1 Midorigaoka Higasi Nijo, Asahikawa, Hokkaido 0788510, Japan
[6] Gifu Univ Hosp, Div Clin Lab, 1-1 Yanagido, Gifu 5011194, Japan
基金
日本学术振兴会;
关键词
UCP1; obesity; CREG1; beige adipocyte; BAT; BROWN ADIPOSE-TISSUE; BEIGE FAT; E1A-STIMULATED GENES; CELLULAR REPRESSOR; PROTEIN; WHITE; ADIPOCYTES;
D O I
10.1093/jb/mvab106
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Brown and beige adipocytes, which express thermogenic uncoupling protein-1 (UCP1), stimulate glucose and lipid metabolism, improving obesity and metabolic diseases such as type 2 diabetes and hyperlipidemia. Overexpression of cellular repressor of E1A-stimulated genes 1 (CREG1) promotes adipose tissue browning and inhibits diet-induced obesity (DIO) in mice. In this study, we investigated the effects of CREG1 administration on DIO inhibition and adipose browning. Subcutaneous administration of recombinant CREG1 protein to C57BL/6 mice stimulated UCP1 expression in interscapular brown adipose tissue (IBAT) and improved DIO, glucose tolerance and fatty liver compared with those in phosphate-buffered saline-treated mice. Injection of Creg1-expressing adenovirus into inguinal white adipose tissue (IWAT) significantly increased browning and mRNA expression of beige adipocyte marker genes compared with that in mice injected with control virus. The effect of Creg1 induction on beige adipocyte differentiation was supported in primary culture using preadipocytes isolated from IWAT of Creg1-transgenic mice compared with that of wild-type mice. Our results indicate a therapeutic effect of CREG1 on obesity and its associated pathology and a potential of CREG1 to stimulate brown/beige adipocyte formation.
引用
收藏
页码:63 / 73
页数:11
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