Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice.
Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice.
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DOI：
10.1371/journal.pone.0012057
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发表时间：
2010-08-10
期刊：
影响因子：
3.7
通讯作者：
Stephanopoulos G
中科院分区：
文献类型：
--
作者：
Noguchi Y;Nishikata N;Shikata N;Kimura Y;Aleman JO;Young JD;Koyama N;Kelleher JK;Takahashi M;Stephanopoulos G
虽然膳食中生酮必需氨基酸(KAA)的含量调节了肝脏脂质的积累，但KAA与脂质代谢之间的分子相互作用尚未完全阐明。在不改变碳水化合物和脂肪含量的前提下，用5种主要游离氨基酸(亮氨酸、异亮氨酸、Val、赖氨酸和苏氨酸)部分替代日粮蛋白质，设计出高必需氨基酸(E/N)比(E/N)的日粮。这种高KAA饮食对饮食诱导的肝脏脂肪变性和全动物胰岛素抵抗的预防效果进行了评估。C57B6小鼠饲喂高脂饲料，高胰岛素ob/ob小鼠饲喂高脂或高蔗糖饲料。高KAA饮食改善了肝脏脂肪变性，减少了从头脂肪生成(DNL)通量，并减少了成脂基因的表达。在C57B6小鼠中，高KAA饮食降低了餐后胰岛素分泌，改善了糖耐量，同时恢复了被高脂饮食抑制的肌肉胰岛素信号蛋白的表达。脂毒性代谢物及其合成通量也参考胰岛素抵抗进行了评估。高KAA饮食降低了肌肉和肝脏神经酰胺，这两个方面都是通过减少饮食中的脂肪并入肌肉神经酰胺和阻止DNL衍生的脂肪酸并入肝脏神经酰胺。我们的结果表明，膳食中摄入KAA可通过调节脂质合成途径改善肝脏脂肪变性和胰岛素抵抗。
Although dietary ketogenic essential amino acid (KAA) content modifies accumulation of hepatic lipids, the molecular interactions between KAAs and lipid metabolism are yet to be fully elucidated. We designed a diet with a high ratio (E/N) of essential amino acids (EAAs) to non-EAAs by partially replacing dietary protein with 5 major free KAAs (Leu, Ile, Val, Lys and Thr) without altering carbohydrate and fat content. This high-KAA diet was assessed for its preventive effects on diet-induced hepatic steatosis and whole-animal insulin resistance. C57B6 mice were fed with a high-fat diet, and hyperinsulinemic ob/ob mice were fed with a high-fat or high-sucrose diet. The high-KAA diet improved hepatic steatosis with decreased de novo lipogensis (DNL) fluxes as well as reduced expressions of lipogenic genes. In C57B6 mice, the high-KAA diet lowered postprandial insulin secretion and improved glucose tolerance, in association with restored expression of muscle insulin signaling proteins repressed by the high-fat diet. Lipotoxic metabolites and their synthetic fluxes were also evaluated with reference to insulin resistance. The high-KAA diet lowered muscle and liver ceramides, both by reducing dietary lipid incorporation into muscular ceramides and preventing incorporation of DNL-derived fatty acids into hepatic ceramides. Our results indicate that dietary KAA intake improves hepatic steatosis and insulin resistance by modulating lipid synthetic pathways.
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影响因子：
56.9
作者：
Cota, D;Proulx, K;Seeley, RJ
通讯作者：
Seeley, RJ
影响因子：
7.7
作者：
Krebs, M;Krssak, M;Roden, M
通讯作者：
Roden, M
DOI：
10.1152/ajpendo.00211.2001
发表时间：
2002-03-01
影响因子：
5.1
作者：
Bassilian, S;Ahmed, S;Lee, WNP
通讯作者：
Lee, WNP
DOI：
10.1152/ajpendo.2000.279.2.e425
发表时间：
2000-08-01
影响因子：
5.1
作者：
Lee, WNP;Bassilian, S;Boros, LG
通讯作者：
Boros, LG
影响因子：
3.5
作者：
Blázquez, C;Geelen, MJH;Guzmán, M
通讯作者：
Guzmán, M