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

短链脂肪酸（SCFA）是反刍动物的主要能量来源，是瘤胃厌氧发酵的产物。提高日粮的发酵性可以提高短链脂肪酸的产量和动物生产力（18），短链脂肪酸的吸收可以稳定瘤胃环境(6)。然而，调控瘤胃上皮（RE）对短链脂肪酸吸收的因素尚不清楚。瘤胃中有游离脂肪酸受体（FFA） 2和3（39）以及toll样受体（TLR） 2和4（22）的表达。在结肠中，FFA2和FFA3已经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（37），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RE的定位。TLR2和4在RE中表达（22），据报道，刺激TLR可减少游离脂肪酸摄取，降低脂肪细胞的脂质代谢（11）；目前尚不清楚在RE中是否也会出现类似的结果。假设是光腔感应机制调节RE中短链脂肪酸的吸收和代谢。目标是：1)表征RE调控短链脂肪酸吸收和代谢的潜在光感机制；2)阐明光感机制对RE对短链脂肪酸吸收和代谢的调节作用；3)评价饲粮处理是否能诱导光感机制的表达和活性变化。为了实现这些目标，我们将招募两名博士生进行一系列的研究，其中一名博士生专注于模式识别受体（PRR），如TLR，另一名专注于肠道营养受体（LNR）。本研究将利用PCR和免疫组织化学技术确定PRR和LNR在反刍动物胃肠道中的定位和表达。体外分离的RE细胞研究将用于评估PRR和LNR的激动剂和拮抗剂对SCFA代谢的作用，并通过使用室实验来研究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的血流量和内脏代谢。该研究项目将提供关于短链脂肪酸吸收代谢调控机制的新信息，并可能通过增加短链脂肪酸吸收来开发新的化合物，以提高反刍动物的效率和健康

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.**