The endocannabinoid system in controlling feed intake and energy balance during the transition from late pregnancy to early lactation of dairy cows

在从妊娠晚期到哺乳早期的过渡过程中，高产奶牛通常会经历负能量平衡，这是因为采食量增加不足，而且产奶所需的能量很大。因此，母亲会调动她们体内的脂肪储备，但通常动员的脂肪越多，产后摄食量增加的幅度就越小。水坝将受益于增加饲料摄入量和减少体内脂肪动员，以最大限度地减少动员脂肪在肝脏中的沉积。到目前为止，大量的代谢物和激素对减少采食量的影响已经在文献中得到了描述，然而，直到今天，关于反刍动物在哺乳期早期显著促进采食量的内源信号还知之甚少。刺激摄食量而限制脂肪分解的显著信号是通过内源性大麻素触发的。在这类物质中，N-花生四烯基乙醇胺(AEA)被认为具有最强的摄食刺激作用。因此，本项目的目的是检验以下假设：1.内源性大麻素信号促进产后采食量，但高水平的脂肪动员会刺激内源性大麻素的降解，从而产生食欲作用。2.腹腔注射AEA通过增加下丘脑促食欲素信号通路和刺激舌汗味感受器增加采食量来改善泌乳早期奶牛的能量平衡。3.外周注射AEA可减少脂肪组织和乳腺中的脂肪分解，增加脂肪生成，从而降低哺乳期早期的肝脏脂肪含量。通过追求这些目标，我们希望阐明内源性大麻素介导的信号转导在妊娠晚期到哺乳早期的生理调节，并描绘改善早期哺乳奶牛能量平衡和健康状况的方法。

During the transition from late pregnancy to early lactation, high producing dairy cows usually experience a negative energy balance due to insufficient increase in feed intake and the enormous energy requirements for milk production. As a consequence, mothers mobilize their body fat reserves, but as more fat is usually mobilized the lower is the postparturient increase in feed intake. Dams would benefit from an increased level of feed intake and reduced body fat mobilization to minimize deposition of mobilized fat in liver. So far, the effect of numerous metabolites and hormones on the reduction of feed intake has been described in literature, however, until today there is only marginal knowledge on endogenous signals significantly promoting feed intake of ruminants during the early lactation period. Prominent signaling stimulating feed intake while confining lipolysis is triggered through endocannabinoids. Among this substance class, N-arachidonoylethanolamine (AEA) has been described to exert one of the strongest feed intake stimulating effects. Therefore, the objective of the present project is to test the hypotheses that: 1. Endocannabinoids signal to promote feed intake postpartum, but high extent of fat mobilisation stimulate the degradation of endocannabinoids and thus their orexigenic action. 2. Intraperitoneal AEA administration improves energy balance of early lactating dairy cows by increasing feed intake involving increased hypothalamic orexigenic signaling and stimulation of lingual sweat taste receptors. 3. Peripheral AEA administration reduces lipolysis and increases lipogenesis in adipose tissue and mammary gland, thereby reducing liver fat content in early lactation. By pursuing these aims we expect to elucidate the physiological regulation of endocannabinoid-mediated signaling during the transition from late pregnancy to early lactation, and to depict ways of improving energy balance and health status of early lactating dairy cows.