Effect of circulating glucagon and free fatty acids on hepatic FGF21 production in dairy cows
Effect of circulating glucagon and free fatty acids on hepatic FGF21 production in dairy cows
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DOI：
10.1152/ajpregu.00197.2017
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发表时间：
2017-11-01
影响因子：
2.8
通讯作者：
Boisclair, Yves R.
中科院分区：
文献类型：
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作者：
Caixeta, Luciano S.;Giesy, Sarah L.;Boisclair, Yves R.
现代奶牛满足能量需求的早期泌乳的呼吁动物驱动的机制，以增加使用的脂质储备。在这种情况下，我们最近报道，成纤维细胞生长因子-21（FGF 21），一种激素所需的有效利用脂质储备的啮齿动物，是上调围产期奶牛。泌乳早期血浆FGF 21增加与胰高血糖素（GCG）和非酯化脂肪酸（NEFA）循环浓度升高一致。为了评估这些因素在调节FGF 21中的相对贡献，在能量充足、非妊娠、非泌乳奶牛中进行了两个实验。在第一项研究中，在72小时内每8小时给奶牛注射一次生理盐水或GCG。GCG使肝脏FGF 21 mRNA平均增加了5倍，但对血浆FGF 21没有影响。在第二项研究中，奶牛输注并注射生理盐水，输注Intraperoid并注射生理盐水，或输注Intraperoid并注射GCG。输注和注射分别在16小时内静脉内和每8小时皮下给药。胰岛素输注使血浆NEFA在3小时内从92 μ M增加到550 μ M，6小时后使血浆FGF 21从1.3 ng/ml增加到> 11 ng/ml;肝脏中FGF 21 mRNA增加了34倍，但脂肪组织中保持不变。在Intraperoid输注期间注射GCG对血浆NEFA、肝脏FGF 21 mRNA或血浆FGF 21没有额外影响。这些数据表明，血浆NEFA是引发肝脏生成和泌乳早期FGF 21循环浓度增加的关键因素。
Modern dairy cows meet the energy demand of early lactation by calling on hormonally driven mechanisms to increase the use of lipid reserves. In this context, we recently reported that fibroblast growth factor-21 (FGF21), a hormone required for efficient use of lipid reserves in rodents, is upregulated in periparturient dairy cows. Increased plasma FGF21 in early lactation coincides with elevated circulating concentrations of glucagon (GCG) and nonesterified fatty acids (NEFA). To assess the relative contribution of these factors in regulating FGF21, two experiments were performed in energy-sufficient, nonpregnant, nonlactating dairy cows. In the first study, cows were injected with saline or GCG every 8 h over a 72-h period. GCG increased hepatic FGF21 mRNA by an average of fivefold over matched controls but had no effect on plasma FGF21. In the second study, cows were infused and injected with saline, infused with Intralipid and injected with saline, or infused with Intralipid and injected with GCG. Infusions and injections were administered intravenously over 16 h and subcutaneously every 8 h, respectively. Intralipid infusion increased plasma NEFA from 92 to 550 mu M within 3 h and increased plasma FGF21 from 1.3 to > 11 ng/ml 6 h later; FGF21 mRNA increased by 34-fold in liver but remained invariant in adipose tissue. GCG injections during the Intralipid infusion had no additional effects on plasma NEFA, liver FGF21 mRNA, or plasma FGF21. These data implicate plasma NEFA as a key factor triggering hepatic production and increased circulating concentrations of FGF21 in early lactation.