胆汁酸如何调控饱足感
创作:szx 审核:szx 2020年03月11日
  • Cyp8b1是产生12α-羟基胆汁酸必需的酶,Cyp8b1敲除小鼠的胆汁酸水平正常但胆汁酸组成显著改变;
  • Cyp8b1敲除小鼠的进食量显著少于野生型小鼠,导致其体重降低;
  • Cyp8b1敲除导致的小鼠空肠中油酰乙醇胺水平降低,后者可提升饱腹感(satiety);
  • Cyp8b1敲除抑制脂肪水解,脂肪水解产物2-单酰甘油通过激活GPR119诱导肠激素GLP-1及PYY以减缓胃排空,以提升饱足感(satiation);
  • GPR119缺失可恢复Cyp8b1敲除小鼠的胃排空、食物摄取及体重。
主编推荐语
szx
胆汁酸调节肠道对脂质的吸收及代谢,但胆汁酸对脂质调节的饱食感与饱腹感有何影响尚未明确。来自Gut上发表的一项最新研究,利用胆汁酸水平正常但胆汁酸组成失调的Cyp8b1敲除小鼠,发现其进食量显著减少且体重降低。机制上,Cyp8b1敲除导致的胆汁酸组成失调并非通过影响饱腹感(satiety),而是通过促进饱足感(satiation)的产生以减少小鼠的进食。具体而言,Cyp8b1敲除抑制了脂肪水解,产生的脂肪水解产物2-单酰甘油可激活GPR119,从而诱导肠激素GLP-1及PYY的产生以减缓胃排空,从而提升饱足感。该研究提示,通过靶向Cyp8b1等方式调控胆汁酸组成,或是治疗肥胖或糖尿病等代谢疾病的潜在策略。
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Gut [IF:19.819]

Bile acid composition regulates GPR119-dependent intestinal lipid sensing and food intake regulation in mice

胆汁酸组成调节小鼠的GPR119依赖性肠道脂质感知及食物摄取调节

10.1136/gutjnl-2019-319693

2020-02-28, Article

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Objectives : 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.
Design: 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.
Results : 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.
Conclusion: BAs regulate gastric emptying and satiation by determining fat-dependent GPR119 activity in distal intestine.

First Authors:
Sei Higuchi

Correspondence Authors:
Rebecca Haeusler

All Authors:
Sei Higuchi,Tiara Rinjani Ahmad,Donovan A Argueta,Pedro A Perez,Chen Zhao,Gary J Schwartz,Nicholas DiPatrizio,Rebecca Haeusler

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