Martens Holger
Institute of Veterinary Physiology, Free University of Berlin, Oertzenweg 19b, 14163 Berlin, Germany.
Animals (Basel). 2023 Oct 4;13(19):3097. doi: 10.3390/ani13193097.
The continued increase in milk production during the last century has not been accompanied by an adequate dry matter intake (DMI) by cows, which therefore experience a negative energy balance (NEB). NEB is low and of minor importance at low milk yield (MY), such as for the nutrition of one calf, and under these circumstances is considered "natural". MY and low DMI around parturition are correlated and are the reason for the genetic correlation between increasing MY and increasing NEB up to 2000 MJ or more for 2-3 months postpartum in high-genetic-merit dairy cows. The extension and duration of NEB in high-producing cows cannot be judged as "natural" and are compensated by the mobilization of nutrients, particularly of fat. The released non-esterified fatty acids (NEFAs) overwhelm the metabolic capacity of the cow and lead to the ectopic deposition of NEFAs as triglycerides (TGs) in the liver. The subsequent lipidosis and the concomitant hampered liver functions cause subclinical and clinical ketosis, both of which are associated with "production diseases", including oxidative and endoplasmatic stress, inflammation and immunosuppression. These metabolic alterations are regulated by homeorhesis, with the priority of the physiological function of milk production. The prioritization of one function, namely, milk yield, possibly results in restrictions in other physiological (health) functions under conditions of limited resources (NEB). The hormonal framework for this metabolic environment is the high concentration of growth hormone (GH), the low concentration of insulin in connection with GH-dependent insulin resistance and the low concentration of IGF-1, the so-called GH-IGF-1 axis. The fine tuning of the GH-IGF-1 axis is uncoupled because the expression of the growth hormone receptor (GHR-1A) in the liver is reduced with increasing MY. The uncoupled GH-IGF-1 axis is a serious impairment for the GH-dependent stimulation of gluconeogenesis in the liver with continued increased lipolysis in fat tissue. It facilitates the pathogenesis of lipidosis with ketosis and, secondarily, "production diseases". Unfortunately, MY is still increasing at inadequate DMI with increasing NEB and elevated NEFA and beta-hydroxybutyric acid concentrations under conditions of low glucose, thereby adding health risks. The high incidences of diseases and of early culling and mortality in dairy cows are well documented and cause severe economic problems with a waste of resources and a challenge to the environment. Moreover, the growing public concerns about such production conditions in agriculture can no longer be ignored.
在上个世纪，奶牛产奶量持续增加，但奶牛的干物质摄入量（DMI）却未相应增加，因此奶牛处于负能量平衡（NEB）状态。在低产奶量（MY）情况下，如仅为一头小牛提供营养时，负能量平衡程度较低且影响较小，在这种情况下被认为是“自然的”。产奶量和分娩前后较低的干物质摄入量相关，这也是高产奶牛产后2至3个月内产奶量增加与负能量平衡增加至2000兆焦耳或更多之间存在遗传相关性的原因。高产奶牛负能量平衡的延长和持续时间不能被判定为“自然的”，需要通过营养物质的动员，特别是脂肪的动员来补偿。释放出的非酯化脂肪酸（NEFAs）超出了奶牛的代谢能力，导致非酯化脂肪酸以甘油三酯（TGs）的形式异位沉积在肝脏中。随后发生的脂肪变性以及随之而来的肝功能受损会引发亚临床和临床酮病，这两种情况都与“生产疾病”相关，包括氧化应激和内质网应激、炎症和免疫抑制。这些代谢变化受同态调节，以产奶生理功能为优先。在资源有限（负能量平衡）的情况下，对一种功能（即产奶量）的优先考虑可能会导致其他生理（健康）功能受到限制。这种代谢环境的激素框架是生长激素（GH）浓度高、与生长激素依赖性胰岛素抵抗相关的胰岛素浓度低以及胰岛素样生长因子-1（IGF-1）浓度低，即所谓的GH-IGF-1轴。随着产奶量增加，肝脏中生长激素受体（GHR-1A）的表达降低，导致GH-IGF-1轴的精细调节失调。失调的GH-IGF-1轴严重损害了生长激素依赖性肝脏糖异生的刺激作用，同时脂肪组织中的脂肪分解持续增加。这促进了脂肪变性合并酮病的发病机制，进而引发“生产疾病”。不幸的是，在干物质摄入量不足、负能量平衡增加、非酯化脂肪酸和β-羟基丁酸浓度升高且葡萄糖水平较低的情况下，产奶量仍在增加，从而增加了健康风险。奶牛疾病、早期淘汰和死亡率高的情况有充分记录，会造成严重的经济问题，浪费资源并对环境构成挑战。此外，公众对农业这种生产条件的日益关注再也不能被忽视。
