Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
Division of Biomedical Sciences, University of California Riverside, Riverside, California, USA.
Gut. 2020 Sep;69(9):1620-1628. doi: 10.1136/gutjnl-2019-319693. Epub 2020 Feb 28.
Lipid mediators in the GI tract regulate satiation and satiety. Bile acids (BAs) regulate the absorption and metabolism of dietary lipid in the intestine, but their effects on lipid-regulated satiation and satiety are completely unknown. Investigating this is challenging because introducing excessive BAs or eliminating BAs strongly impacts GI functions. We used a mouse model (Cyp8b1 mice) with normal total BA levels, but alterations in the composition of the BA pool that impact multiple aspects of intestinal lipid metabolism. We tested two hypotheses: BAs affect food intake by (1) regulating production of the bioactive lipid oleoylethanolamide (OEA), which enhances satiety; or (2) regulating the quantity and localisation of hydrolysed fat in small intestine, which controls gastric emptying and satiation.
We evaluated OEA levels, gastric emptying and food intake in wild-type and Cyp8b1 mice. We assessed the role of the fat receptor GPR119 in these effects using Gpr119 mice.
Cyp8b1 mice on a chow diet showed mild hypophagia. Jejunal OEA production was blunted in Cyp8b1 mice, thus these data do not support a role for this pathway in the hypophagia of Cyp8b1 mice. On the other hand, Cyp8b1 deficiency decreased gastric emptying, and this was dependent on dietary fat. GPR119 deficiency normalised the gastric emptying, gut hormone levels, food intake and body weight of Cyp8b1 mice.
BAs regulate gastric emptying and satiation by determining fat-dependent GPR119 activity in distal intestine.
胃肠道中的脂质介质可调节饱腹感和饥饿感。胆汁酸（BAs）可调节肠道内膳食脂质的吸收和代谢，但它们对脂质调节饱腹感和饥饿感的影响尚不清楚。研究这一点具有挑战性，因为引入过多的 BAs 或消除 BAs 会强烈影响胃肠道功能。我们使用了一种具有正常总 BA 水平但 BA 池组成发生改变的小鼠模型（Cyp8b1 小鼠），这种改变会影响肠道脂质代谢的多个方面。我们检验了两个假设：BAs 通过（1）调节生物活性脂质油酰乙醇酰胺（OEA）的产生来影响食物摄入，而 OEA 可增强饱腹感；或（2）调节小肠中水解脂肪的数量和定位来控制胃排空和饱腹感。
我们评估了野生型和 Cyp8b1 小鼠中的 OEA 水平、胃排空和食物摄入。我们使用 Gpr119 小鼠评估了脂肪受体 GPR119 在这些作用中的作用。
进食标准饮食的 Cyp8b1 小鼠表现出轻度摄食量减少。Cyp8b1 小鼠的空肠 OEA 产生受到抑制，因此这些数据不支持该途径在 Cyp8b1 小鼠摄食减少中的作用。另一方面，Cyp8b1 缺乏症降低了胃排空，这取决于饮食中的脂肪。GPR119 缺乏症使 Cyp8b1 小鼠的胃排空、肠道激素水平、食物摄入和体重恢复正常。
BAs 通过确定远端肠道中脂肪依赖性 GPR119 活性来调节胃排空和饱腹感。
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