Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity.
Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity.
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DOI：
10.4137/grsb.s14116
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Loor JJ
中科院分区：
文献类型：
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作者：
Khan MJ;Jacometo CB;Graugnard DE;Corrêa MN;Schmitt E;Cardoso F;Loor JJ
在妊娠的最后45天期间，研究了饲喂对照（CON，1.34 Mcal/kg）或高能量（过度饲喂（OVE），1.62 Mcal/kg）饮食的奶牛的肝代谢基因网络。在分娩前后的-14，7，14和30天，对共57个靶基因进行了评价，包括PPARα靶点/辅助调节因子、肝细胞因子、生长激素（GH）/胰岛素样生长因子1（IGF-1）轴、脂肪生成和脂蛋白代谢。与CON奶牛相比，OVE奶牛产后处于更多的负能量平衡（NEB），血清非酯化脂肪酸（NEFA）、β-羟基丁酸酯（BHBA）和肝脏三酰甘油（TAG）浓度更高。乳汁合成率无差异。OVE奶牛的肝脏通过上调脂肪酸氧化和生酮途径中的PPARα靶点表达以及沿着促凋亡基因对产后NEB作出反应。肝细胞因子（成纤维细胞生长因子21（FGF 21）、血管生成素样4（ANGPTL 4））和载脂蛋白A-V（APOA 5）在产后在OVE中的上调程度大于CON。OVE导致更高的血胰岛素分泌、更低的NEFA：胰岛素和更高的脂肪生成基因表达，表明胰岛素敏感性未受损。在饲喂OVE的奶牛中，APOB、MTTP和PNPLA 3缺乏变化，加上产后PLIN 2上调，导致TAG积累。NEFA和FGF 21与OVE的产后反应支持这种肝细胞因子在降低脂肪胰岛素敏感性中的作用。
Hepatic metabolic gene networks were studied in dairy cattle fed control (CON, 1.34 Mcal/kg) or higher energy (overfed (OVE), 1.62 Mcal/kg) diets during the last 45 days of pregnancy. A total of 57 target genes encompassing PPARα-targets/co-regulators, hepatokines, growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, lipogenesis, and lipoprotein metabolism were evaluated on −14, 7, 14, and 30 days around parturition. OVE versus CON cows were in more negative energy balance (NEB) postpartum and had greater serum non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and liver triacylglycerol (TAG) concentrations. Milk synthesis rate did not differ. Liver from OVE cows responded to postpartal NEB by up-regulating expression of PPARα-targets in the fatty acid oxidation and ketogenesis pathways, along with gluconeogenic genes. Hepatokines (fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4)) and apolipoprotein A-V (APOA5) were up-regulated postpartum to a greater extent in OVE than CON. OVE led to greater blood insulin prepartum, lower NEFA:insulin, and greater lipogenic gene expression suggesting insulin sensitivity was not impaired. A lack of change in APOB, MTTP, and PNPLA3 coupled with upregulation of PLIN2 postpartum in cows fed OVE contributed to TAG accumulation. Postpartal responses in NEFA and FGF21 with OVE support a role of this hepatokine in diminishing adipose insulin sensitivity.