Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice

被引：48

作者：

Carino, Adriana ^{[1
]}

Cipriani, Sabrina ^{[2
]}

Marchiano, Silvia ^{[1
]}

Biagioli, Michele ^{[1
]}

Scarpelli, Paolo ^{[5
]}

Zampella, Angela ^{[3
]}

Monti, Maria Chiara ^{[4
]}

Fiorucci, Stefano ^{[1
]}

机构：

[1] Univ Perugia, Dept Surg & Biomed Sci, Perugia, Italy

[2] Univ Perugia, Dept Med, Perugia, Italy

[3] Univ Naples Federico II, Dept Pharm, Naples, Italy

[4] Univ Salerno, Dept Pharm, Salerno, Italy

[5] Univ Perugia, Dept Expt Med, Perugia, Italy

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

FATTY LIVER-DISEASE; BEIGE ADIPOCYTES; MOUSE; EXPRESSION; STEATOSIS; CELL;

D O I：

10.1038/s41598-017-13102-y

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：

Gpbar1 is a bile acid activated receptor for secondary bile acids. Here we have investigated the mechanistic role of Gpbar1 in the regulation of adipose tissues functionality in a murine model of steatohepatitis (NASH). Feeding wild type and Gpbar1(-/-) mice with a high fat diet-fructose (HFD-F) lead to development of NASH-like features. Treating HFD-F mice with 6 beta-ethyl-3a, 7b-dihydroxy-5b-cholan-24-ol (BAR501), a selective Gpbar1-ligand, reversed insulin resistance and histologic features of NASH, increased the weight of epWAT and BAT functionality and promoted energy expenditure and the browning of epWAT as assessed by measuring expression of Ucp1 and Pgc-1 alpha. The beneficial effects of BAR501 were lost in Gpbar1(-/-) mice. In vitro, BAR501 promoted the browning of 3T3-L1 cells a preadipocyte cell line and recruitment of CREB to the promoter of Pgc-1a. In conclusion, Gpbar1 agonism ameliorates liver histology in a rodent model of NASH and promotes the browning of white adipose tissue.

引用

页数：13

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