Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows
Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows
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DOI：
10.1152/physiolgenomics.00188.2007
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发表时间：
2007-12-19
影响因子：
4.6
通讯作者：
Lewin, Harris A.
中科院分区：
文献类型：
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作者：
Loor, Juan J.;Everts, Robin E.;Lewin, Harris A.
奶牛在分娩后非常容易患上肝纤维化和酮病，这对农民来说是代价高昂的疾病。使用由13，257个注释的寡核苷酸组成的牛微阵列平台来研究营养诱导的酮症的肝脏基因网络。在产后第5天，14头荷斯坦奶牛被随机分配到酮症诱导组（n = 7）或对照组（n = 7）。酮症诱导组奶牛以第4天摄入量的50%饲喂，直至出现临床酮症体征，对照组奶牛在整个给药期间自由采食。在产后10-14天（酮症）或14天（对照）对肝脏进行活检。限食增加了血液中非酯化脂肪酸和β-羟基丁酸的浓度，但降低了葡萄糖。肝脏三酰甘油浓度也增加。共有2,415个基因被酮症改变（错误发现率= 0.05）。抗氧化途径分析显示与氧化磷酸化、蛋白质泛素化和泛醌生物合成相关的基因在酮症中下调。其他分子适应包括与细胞因子信号传导、脂肪酸摄取/转运和脂肪酸氧化相关的基因和核受体的上调。酮症过程中下调的基因包括与胆固醇代谢、生长激素信号、质子转运和脂肪酸去饱和相关的几个基因。饲料限制和酮症导致先前未被认识到的基因网络表达的改变，这些改变是关键细胞功能和离散代谢事件的基础。这些反应可能有助于解释产后早期奶牛对摄食量减少的充分记录的生理适应，因此，提供了可能有助于预防和治疗肝纤维化和酮病的分子靶点。
Dairy cows are highly susceptible after parturition to developing liver lipidosis and ketosis, which are costly diseases to farmers. A bovine microarray platform consisting of 13,257-annotated oligonucleotides was used to study hepatic gene networks underlying nutrition-induced ketosis. On day 5 postpartum, 14 Holstein cows were randomly assigned to ketosis-induction (n = 7) or control (n = 7) groups. Cows in the ketosis-induction group were fed at 50% of day 4 intake until they developed signs of clinical ketosis, and cows in the control group were fed ad libitum throughout the treatment period. Liver was biopsied at 10-14 (ketosis) or 14 days postpartum (controls). Feed restriction increased blood concentrations of nonesterified fatty acids and beta- hydroxybutyrate, but decreased glucose. Liver triacylglycerol concentration also increased. A total of 2,415 genes were altered by ketosis (false discovery rate = 0.05). Ingenuity Pathway Analysis revealed downregulation of genes associated with oxidative phosphorylation, protein ubiquitination, and ubiquinone biosynthesis with ketosis. Other molecular adaptations included upregulation of genes and nuclear receptors associated with cytokine signaling, fatty acid uptake/transport, and fatty acid oxidation. Genes downregulated during ketosis included several associated with cholesterol metabolism, growth hormone signaling, proton transport, and fatty acid desaturation. Feed restriction and ketosis resulted in previously unrecognized alterations in gene network expression underlying key cellular functions and discrete metabolic events. These responses might help explain well-documented physiological adaptations to reduced feed intake in early postpartum cows and, thus, provide molecular targets that might be useful in prevention and treatment of liver lipidosis and ketosis.