Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
J Dairy Sci. 2010 Jun;93(6):2404-18. doi: 10.3168/jds.2009-2716.
Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists increase fatty acid oxidation in liver of nonruminants. If similar effects occur in dairy cattle, enhanced hepatic oxidative capacity could decrease circulating nonesterified fatty acids and hepatic triacylglycerol accumulation in periparturient cows. The objectives of this study were 1) to determine whether partitioning of fatty acid metabolism by liver slices from weaned Holstein calves treated with PPARalpha agonists in vivo is altered compared with partitioning by liver slices from control (untreated) calves, and 2) to measure in vitro metabolism of palmitate and oleate by bovine liver slices and relate these to mRNA abundance for key enzymes. Weaned male Holstein calves (7 wk old; n=15) were assigned to 1 of 3 groups for a 5-d treatment period: control (untreated), clofibrate (62.5 mg/kg of BW), or fish oil (250 mg/kg of BW). Calves treated with clofibrate consumed less dry matter. Body weight, liver weight, liver weight:body weight ratio, blood nonesterified fatty acids, beta-hydroxybutyrate, and liver composition were not significantly different among treatments. Liver slices were incubated for 2, 4, and 8 h to determine in vitro conversion of [1-(14)C] palmitate and [1-(14)C] oleate to CO(2), acid-soluble products, esterified products, and total metabolism. In liver slices incubated for 8 h, conversion of palmitate to CO(2) was greater for calves treated with clofibrate compared with control calves or calves treated with fish oil. Conversion of palmitate to esterified products, total palmitate metabolism, and metabolism of oleate were not different among treatments. Conversion of palmitate to CO(2) was greater than that from oleate for all treatments, but rates of total metabolism did not differ. Clofibrate increased or tended to increase liver expression of several PPARalpha target genes involved in fatty acid oxidation (e.g., ACADVL, ACOX1, CPT1A), whereas fish oil did not significantly affect genes associated with fatty acid oxidation but tended to increase DGAT1. Overall, our data indicated that bovine liver responded to clofibrate treatment but not fish oil, although increases in hepatic lipid metabolism were much less than those reported in rodents treated with clofibrate or fish oil. Applications of PPARalpha agonists may be of interest to increase the rate of hepatic fatty acid oxidation and decrease triacylglycerol accumulation in periparturient dairy cows.
过氧化物酶体增殖物激活受体-α（PPARα）激动剂可增加非反刍动物肝脏中的脂肪酸氧化。如果这种类似的作用发生在奶牛身上，那么增强肝氧化能力可以减少围产期奶牛循环中非酯化脂肪酸和肝三酰甘油的积累。本研究的目的是：1）确定与对照（未处理）小牛的肝切片相比，经体内 PPARα 激动剂处理的断奶荷斯坦小牛的肝切片中脂肪酸代谢的分配是否发生改变，以及 2）测量牛肝切片中棕榈酸和油酸的体外代谢，并将其与关键酶的 mRNA 丰度相关联。将 7 周龄断奶雄性荷斯坦小牛（n=15）分配到 3 个处理组中的 1 个，进行为期 5 天的处理期：对照（未处理）、氯贝丁酸（62.5mg/kg BW）或鱼油（250mg/kg BW）。用氯贝丁酸处理的小牛消耗的干物质较少。体重、肝重、肝重/体重比、血液非酯化脂肪酸、β-羟丁酸和肝组成在处理之间没有显著差异。将肝切片孵育 2、4 和 8 h，以确定体外[1-（14）C]棕榈酸和[1-（14）C]油酸转化为 CO2、酸溶性产物、酯化产物和总代谢产物。在孵育 8 h 的肝切片中，用氯贝丁酸处理的小牛转化为 CO2 的棕榈酸比对照小牛或用鱼油处理的小牛多。棕榈酸转化为酯化产物、总棕榈酸代谢和油酸代谢在处理之间没有差异。所有处理中棕榈酸转化为 CO2 的速率均大于油酸，但总代谢速率没有差异。氯贝丁酸增加或倾向于增加与脂肪酸氧化相关的几个 PPARα 靶基因的肝表达（例如，ACADVL、ACOX1、CPT1A），而鱼油对与脂肪酸氧化相关的基因没有显著影响，但倾向于增加 DGAT1。总的来说，我们的数据表明，牛肝对氯贝丁酸处理有反应，但对鱼油没有反应，尽管肝脂质代谢的增加远低于用氯贝丁酸或鱼油处理的啮齿动物报告的增加。应用 PPARα 激动剂可能有助于增加围产期奶牛肝脂肪酸氧化的速率并减少三酰甘油的积累。
