Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats
Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats
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DOI：
10.1186/s12986-020-00477-5
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发表时间：
2020-08-03
影响因子：
4.5
通讯作者：
Kato, Hisanori
中科院分区：
文献类型：
--
作者：
Otani, Lila;Nishi, Hiroki;Kato, Hisanori
背景膳食蛋白质缺乏和氨基酸失衡导致肝脏脂肪蓄积。我们以前证明，只有精氨酸缺乏或总氨基酸缺乏的饮食引起显着的肝甘油三酯（TG）的积累在年轻的Wistar大鼠。在本研究中，我们探讨了这些模型中脂肪肝形成的机制。方法6周龄雄性Wistar大鼠分别饲喂对照饲料（含相当于15%蛋白质的氨基酸混合物）、低总氨基酸饲料（相当于5%蛋白质; 5PAA）和低精氨酸饲料（仅精氨酸含量与5PAA饲料一样低）2周。结果低精氨酸组大鼠肝脏TG蓄积明显高于低总氨基酸组。各组之间肝脏中的脂质消耗率和脂肪酸摄取没有显著差异。相比之下，低总氨基酸饮食增强了肝脏中的胰岛素敏感性和相关信号传导，并增强了从头脂肪生成。低精氨酸饮食还抑制肝脏极低密度脂蛋白分泌，而不影响肝脏胰岛素信号传导和脂肪生成。结论虽然低精氨酸饮食和低氨基酸饮食的精氨酸含量相同，但两种饮食引起脂肪肝的机制完全不同。脂肪生成增强是低蛋白饮食诱导的脂肪肝的主要原因，而极低密度脂蛋白分泌降低则导致低精氨酸饮食诱导的脂肪肝。
Background Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models. Methods We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks. Results Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis. Conclusions Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.