Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice.
Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice.
复制标题
DOI：
10.1038/s41598-017-13102-y
复制
发表时间：
2017-10-20
影响因子：
4.6
通讯作者：
Fiorucci S
中科院分区：
文献类型：
--
作者：
Carino A;Cipriani S;Marchianò S;Biagioli M;Scarpelli P;Zampella A;Monti MC;Fiorucci S
Gpbar 1是胆汁酸激活的二级胆汁酸受体。在此，我们研究了Gpbar 1在脂肪性肝炎（NASH）小鼠模型中调节脂肪组织功能的机制作用。用高脂肪饮食-果糖（HFD-F）喂养野生型和Gpbar 1 −/−小鼠导致NASH样特征的发展。用6β-乙基-3a，7 b-二羟基-5b-胆烷-24-醇（BAR 501）（一种选择性Gpbar 1-配体）治疗HFD-F小鼠，逆转了胰岛素抵抗和NASH的组织学特征，增加了epWAT的重量和BAT功能，并促进了能量消耗和epWAT的布朗宁（通过测量Ucp 1和Pgc-1α的表达进行评估）。BAR 501的有益作用在Gpbar 1 −/−小鼠中丧失。在体外，BAR 501促进前脂肪细胞系3 T3-L1细胞的布朗宁和CREB向Pgc-1α启动子的募集。总之，Gpbar 1激动改善了NASH啮齿动物模型的肝脏组织学，并促进了白色脂肪组织的布朗宁。
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 6β-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-1α. The beneficial effects of BAR501 were lost in Gpbar1−/− mice. In vitro, BAR501 promoted the browning of 3T3-L1 cells a pre-adipocyte cell line and recruitment of CREB to the promoter of Pgc-1α. In conclusion, Gpbar1 agonism ameliorates liver histology in a rodent model of NASH and promotes the browning of white adipose tissue.
登录
查看更多内容
影响因子：
4.6
作者：
Carino A;Cipriani S;Marchianò S;Biagioli M;Santorelli C;Donini A;Zampella A;Monti MC;Fiorucci S
通讯作者：
Fiorucci S
影响因子：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
影响因子：
7.3
作者：
Sepe, Valentina;Renga, Barbara;Fiorucci, Stefano
通讯作者：
Fiorucci, Stefano
影响因子：
3.7
作者：
Renga B;Cipriani S;Carino A;Simonetti M;Zampella A;Fiorucci S
通讯作者：
Fiorucci S
影响因子：
158.5
作者：
Virtanen, Kirsi A.;Lidell, Martin E.;Nuutila, Pirjo
通讯作者：
Nuutila, Pirjo