The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents.

The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents.
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短链脂肪酸丙酸酯通过啮齿动物中的游离脂肪酸受体2刺激GLP-1和PYY分泌。

DOI:
10.1038/ijo.2014.153
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发表时间:
2015-03
影响因子:
4.9
通讯作者:
Frost, G.
Frost, G.
中科院分区:
医学2区
文献类型:
--
作者:
Psichas, A.;Sleeth, M. L.;Murphy, K. G.;Brooks, L.;Bewick, G. A.;Hanyaloglu, A. C.;Ghatei, M. A.;Bloom, S. R.;Frost, G.

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肠激素肽YY(PYY)和胰高血糖素样肽1(GLP-1)急性抑制食欲。短链脂肪酸(SCFA)受体,即游离脂肪酸受体2(FFA 2)存在于结肠肠内分泌L细胞上,并且已表明SCFA在食欲调节中发挥作用。在这里,我们研究了结肠丙酸盐对啮齿动物PYY和GLP-1释放的体外和体内作用,并使用FFA 2基因敲除小鼠研究FFA 2在介导这些作用中的作用。我们使用Wistar大鼠、C57 BL 6小鼠和C57 BL 6背景下的游离脂肪酸受体2敲除(FFA−/−)小鼠,以探索SCFA丙酸盐对PYY和GLP-1释放的影响。采用离体结肠隐窝培养物评价丙酸盐对体外肠激素释放的影响。随后,我们开发了一种体内技术,以评估肠道激素释放到门静脉后,结肠输注丙酸。丙酸盐刺激野生型原代小鼠结肠隐窝培养物中PYY和GLP-1的分泌。这种效应在FFA 2 −/−小鼠的培养物中显著减弱。丙酸盐的结肠内输注升高了大鼠颈静脉血浆和大鼠和小鼠门静脉血浆中的PYY和GLP-1水平。然而,丙酸盐并没有显著刺激FFA 2 −/−小鼠的肠道激素释放。丙酸盐的结肠内给药刺激大鼠和小鼠中GLP-1和PYY的同时释放。这些数据表明,FFA 2缺乏损害SCFA诱导的肠道激素分泌在体外和体内。
The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) acutely suppress appetite. The short chain fatty acid (SCFA) receptor, free fatty acid receptor 2 (FFA2) is present on colonic enteroendocrine L cells, and a role has been suggested for SCFAs in appetite regulation. Here, we characterise the in vitro and in vivo effects of colonic propionate on PYY and GLP-1 release in rodents, and investigate the role of FFA2 in mediating these effects using FFA2 knockout mice. We used Wistar rats, C57BL6 mice and free fatty acid receptor 2 knockout (FFA−/−) mice on a C57BL6 background to explore the impact of the SCFA propionate on PYY and GLP-1 release. Isolated colonic crypt cultures were used to assess the effects of propionate on gut hormone release in vitro. We subsequently developed an in vivo technique to assess gut hormone release into the portal vein following colonic infusion of propionate. Propionate stimulated the secretion of both PYY and GLP-1 from wild-type primary murine colonic crypt cultures. This effect was significantly attenuated in cultures from FFA2−/− mice. Intra-colonic infusion of propionate elevated PYY and GLP-1 levels in jugular vein plasma in rats and in portal vein plasma in both rats and mice. However, propionate did not significantly stimulate gut hormone release in FFA2−/− mice. Intra-colonic administration of propionate stimulates the concurrent release of both GLP-1 and PYY in rats and mice. These data demonstrate that FFA2 deficiency impairs SCFA-induced gut hormone secretion both in vitro and in vivo.
肠道菌群通过短链脂肪酸受体GPR43抑制胰岛素介导的脂肪积累。
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影响因子: 16.6
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期刊: Science (New York, N.Y.)
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影响因子: 4
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