Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.
Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.
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DOI：
10.1136/gutjnl-2014-307913
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发表时间：
2015-11
期刊：
影响因子：
24.5
通讯作者：
Frost G
中科院分区：
文献类型：
--
作者：
Chambers ES;Viardot A;Psichas A;Morrison DJ;Murphy KG;Zac-Varghese SE;MacDougall K;Preston T;Tedford C;Finlayson GS;Blundell JE;Bell JD;Thomas EL;Mt-Isa S;Ashby D;Gibson GR;Kolida S;Dhillo WS;Bloom SR;Morley W;Clegg S;Frost G
结肠微生物群发酵膳食纤维，产生短链脂肪酸。最近的证据表明，短链脂肪酸丙酸酯可能在食欲调节中发挥重要作用。我们假设丙酸盐的结肠递送会增加人类中肽YY（PYY）和胰高血糖素样肽-1（GLP-1）的分泌，并减少超重成人的能量摄入和体重增加。为了研究丙酸盐是否促进PYY和GLP-1分泌，开发了原代培养的人结肠细胞模型。为了将丙酸酯特异性地递送到结肠，我们开发了一种新的菊糖丙酸酯。一项急性随机对照交叉研究被用来评估这种菊糖丙酸酯对能量摄入和血浆PYY和GLP-1浓度的影响。菊粉丙酸酯对体重增加的长期影响随后在一项涉及60名超重成年人的随机对照24周研究中进行了评估。丙酸盐显著刺激人结肠细胞释放PYY和GLP-1。急性摄入10 g菊糖丙酸酯显著增加餐后血浆PYY和GLP-1，并减少能量摄入。 在24周内，10克/天菊糖丙酸酯补充剂显着减少体重增加，腹内脂肪组织分布，肝细胞内脂质含量，并防止在菊糖对照组中观察到的胰岛素敏感性恶化。 这些数据首次证明，增加结肠丙酸盐可以防止超重成年人体重增加。NCT 00750438。
The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. NCT00750438.