Regulation of short-chain fatty acid transport and metabolism across the rumen epithelium

跨瘤胃上皮短链脂肪酸转运和代谢的调节

• 批准号: RGPIN-2016-06525
• 负责人: Penner, Gregory
• 金额: $ 2.26万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684044
• 关键词: Regulation; short; chain; fatty; acid

Short-chain fatty acids (SCFA), a product of anaerobic fermentation in the rumen, are the primary energy source for ruminants. Increasing diet fermentability increases SCFA production and animal productivity(18), with SCFA absorption stabilizing the ruminal environment(6). However, the regulatory factors for SCFA absorption across the rumen epithelium (RE) are not well understood. Expression of free fatty acid receptors (FFA) 2 and 3(39) and toll-like receptors (TLR) 2 and 4(22) have been reported in the rumen. In the colon, FFA2 and FFA3 have been localized in enteroendocrine cells(25). Stimulation of FFA2 and FFA3 by SCFA, stimulates neuroendocrine signalling(37) thereby modulating SCFA absorption. The RE does not contain enteroendocrine cells and therefore, studies to determine localization in the RE are needed. TLR2 and 4 are expressed in the RE(22) and stimulation of TLR has been reported to decrease free fatty acid uptake and reduce lipid metabolism in adipocytes(11); it is not known if similar results occur in the RE. The hypothesis is that luminal sensing mechanisms regulate RE SCFA absorption and metabolism. The objectives are to; 1) characterize potential luminal-sensing mechanisms involved in the regulation of SCFA absorption and metabolism by the RE, 2) elucidate the regulatory role of luminal-sensing mechanisms on the absorption and metabolism of SCFA by the RE, and 3) evaluate whether dietary treatments can induce changes in the expression and activity of luminal-sensing mechanisms. To address these objectives, two PhD students will be recruited to conduct a series of studies with one student focusing on pattern recognition receptors (PRR) such as TLR and the other focusing on luminal nutrient receptors (LNR). The studies will determine the localization and expression of PRR and LNR throughout the ruminant gastrointestinal tract using PCR and immunohistochemistry. In vitro studies with isolated RE cells will be used to evaluate the role of agonists and antagonists of the PRR and LNR on SCFA metabolism and Ussing chamber experiments will be conducted to examine whether PRR and LNR regulate SCFA absorption. Finally, in vivo studies will be conducted to evaluate whether (and how) PRR and LNR regulate blood flow and splanchnic metabolism of SCFA. This research program will provide novel information on regulatory mechanisms for the absorptive metabolism of SCFA and may lead to the development of novel compounds to improve the efficiency, and health of ruminants by increasing SCFA absorption.**

短链脂肪酸(SCFA)是瘤胃厌氧发酵的产物，是反刍动物的主要能量来源。提高饲料发酵性可增加单链脂肪酸产量和动物生产力(18)，单链脂肪酸的吸收稳定瘤胃环境(6)。然而，SCFA通过瘤胃上皮(RE)吸收的调节因素还不是很清楚。自由脂肪酸受体(FFA)2和3(39)和Toll样受体(TLR)2和4(22)在瘤胃中的表达已被报道。在结肠中，FFA2和FFA3定位于肠内分泌细胞(25)。SCFA刺激FFA2和FFA3刺激神经内分泌信号，从而调节SCFA的吸收。RE不含肠内分泌细胞，因此需要研究确定其在RE中的定位。TLR2和4在RE(22)中表达，刺激TLR可减少脂肪细胞对游离脂肪酸的摄取并降低脂肪代谢(11)；目前尚不清楚RE是否也有类似的结果。该假说认为，腔传感机制调节稀土单链脂肪酸的吸收和代谢。这些研究的目的是：1)确定RE对SCFA吸收和代谢的潜在调节机制；2)阐明RE对SCFA的吸收和代谢的调节作用；3)评价饮食处理是否可以诱导光敏机制的表达和活性的变化。为了实现这些目标，将招募两名博士生进行一系列研究，其中一名学生重点研究TLR等模式识别受体(PRR)，另一名学生重点研究鲁米那营养受体(LNR)。本研究将用聚合酶链式反应和免疫组织化学的方法确定PRR和LNR在整个反刍动物胃肠道中的定位和表达。我们将利用分离的RE细胞进行体外研究，以评估PRR和LNR的激动剂和拮抗剂对SCFA代谢的作用，并通过Ussing小室实验来研究PRR和LNR是否调节SCFA的吸收。最后，将进行体内研究，以评估PRR和LNR是否(以及如何)调节SCFA的血流和内脏代谢。这项研究计划将为SCFA吸收代谢的调节机制提供新的信息，并可能导致开发新的化合物，通过增加SCFA的吸收来提高反刍动物的效率和健康。