Lipid metabolism in lactating ruminants

亚油酸（18：2 n-6）和α-亚麻酸（18：3 n-3）是哺乳动物的必需营养素。这些脂肪酸及其代谢产物参与多种生物学功能，例如免疫应答、血液凝固、血管阻力、细胞增殖和分化、酶活性和受体表达。反刍动物，像其他哺乳动物一样，不能合成必需脂肪酸（EFA）;因此，它们必须从饲料中获得。然而，目前没有明确的反刍动物全民教育要求。泌乳奶牛每日所需的量难以确定，原因是：i）瘤胃中生物氢化的膳食EFA比例波动，降低了其吸收可用性; ii）乳脂中分泌的n-6和n-3脂肪酸数量不一，因此无法用于动物代谢。随着EFA的充足供应，18：2 n-6和18：3 n-3被去饱和并延长为不同的代谢产物，这些代谢产物是生理功能和基因表达的重要调节剂。研究表明，食用大量的EFA可能对肝脏代谢和泌乳性能以及泌乳奶牛产生有益影响。然而，数据还不足以确定这些系统的效率提高所需的具体进气量。拟议的研究计划的主要目标是进一步了解EFA在奶牛反刍动物中的代谢。假设是泌乳奶牛中的EFA供应调节肝脏代谢和营养物质向乳腺的输送，以支持乳汁合成。具体目标是：1）探索肝脏和乳腺组织对EFA缺乏的总体适应性; 2）评估18：2 n-6和18：3 n-3在单独或联合供应时对动物生理学和泌乳性能的作用; 3）研究EFA的延长、去饱和和反式氧化过程。泌乳奶牛将饲喂缺乏EFA的饲料。将采集活检以确定对肝脏和乳腺组织转录组的影响，并采集血液样本以确定血浆代谢组。将使用相同的EFA缺陷奶牛模型进一步检查补充18：2 n-6和18：3 n-3对动物生理学的影响。这些EFA的皱胃输注将允许研究它们的代谢（伸长，去饱和）及其对分子和细胞功能的影响，而没有与瘤胃生物氢化的变化速率相关的不确定性。通过创造一个缺陷和控制摄入量，生物氢化和分泌的EFA，拟议的研究计划有可能更精确地针对代谢功能，需要18：2 n-6，18：3 n-3，或其代谢产物。从长远来看，该计划将允许确定泌乳反刍动物对EFA的更精确的饮食需求。

Linoleic acid (18:2 n-6) and alpha-linolenic acid (18:3 n-3) are essential nutrients in mammals. These fatty acids and their metabolites are involved in several biological functions, such as immune response, blood coagulation, vascular resistance, cell proliferation and differentiation, enzyme activities, and receptor expression. Ruminants, like other mammals, are not able to synthesize essential fatty acids (EFA); therefore, they must be obtained from feedstuffs. However, there is currently no defined EFA requirements for ruminants. Daily amounts required for lactating cows are hard to establish due to: i) fluctuating proportions of dietary EFA being biohydrogenated in the rumen, reducing their availability for absorption; and ii) varying quantities of n-6 and n-3 fatty acids being secreted in milk fat, which are therefore not available for animal metabolism. With adequate supply of EFA, 18:2 n-6 and 18:3 n-3 are desaturated and elongated to varying metabolites which are important regulators of physiological functions and gene expression. Studies have shown that consumption of greater quantities of EFA may have beneficial effects on hepatic metabolism and lactation performances and in lactating cows. Nevertheless, data are not conclusive enough to define specific intake requirements for an improved efficiency of these systems. The main objective of the proposed research program is to gain further insight into the metabolism of EFA in dairy ruminants. The hypothesis is that EFA supplies in lactating cows modulate hepatic metabolism and the delivery of nutrients to the mammary gland to support milk synthesis. The specific objectives are to: 1) explore the overall adaptations of liver and mammary tissues to EFA deficiency; 2) assess the role of 18:2 n-6 and 18:3 n-3 on animal physiology and lactation performance, when supplied individually or in combination; and 3) study the process of elongation, desaturation and ß-oxidation of EFA. Lactating cows will be fed an EFA-deficient diet. Biopsies will be harvested to determine the impacts on liver and mammary tissue transcriptomes, and blood samples will be collected to determined plasma metabolome. The same model of EFA-deficient cows will be used to further examine the impact of supplemental 18:2 n-6 and 18:3 n-3 on animal physiology. Abomasal infusion of these EFA will allow to study their metabolism (elongation, desaturation) and their effects on molecular and cellular functions, without the uncertainty related to varying rates of ruminal biohydrogenation. By creating a deficiency and controlling intake, biohydrogenation and secretion of EFA, the proposed research program has the potential to more precisely target the metabolic functions requiring 18:2 n-6, 18:3 n-3, or their metabolites. In the long run, this program will allow to define more precise dietary requirements of EFA in lactating ruminants.