This study tested the hypothesis that elevated L-leucine concentrations in plasma reduce nitric oxide (NO) synthesis by endothelial cells (ECs) and affect adiposity in obese rats. Beginning at four weeks of age, male Sprague-Dawley rats were fed a casein-based low-fat (LF) or high-fat (HF) diet for 15 weeks. Thereafter, rats in the LF and HF groups were assigned randomly into one of two subgroups (n = 8/subgroup) and received drinking water containing either 1.02% L-alanine (isonitrogenous control) or 1.5% L-leucine for 12 weeks. The energy expenditure of the rats was determined at weeks 0, 6, and 11 of the supplementation period. At the end of the study, an oral glucose tolerance test was performed on all the rats immediately before being euthanized for the collection of tissues. HF feeding reduced (P < 0.001) NO synthesis in ECs by 21% and whole-body insulin sensitivity by 19% but increased (P < 0.001) glutamine:fructose-6-phosphate transaminase (GFAT) activity in ECs by 42%. Oral administration of L-leucine decreased (P < 0.05) NO synthesis in ECs by 14%, increased (P < 0.05) GFAT activity in ECs by 35%, and reduced (P < 0.05) whole-body insulin sensitivity by 14% in rats fed the LF diet but had no effect (P > 0.05) on these variables in rats fed the HF diet. L-Leucine supplementation did not affect (P > 0.05) weight gain, tissue masses (including white adipose tissue, brown adipose tissue, and skeletal muscle), or antioxidative capacity (indicated by ratios of glutathione/glutathione disulfide) in LF- or HF-fed rats and did not worsen (P > 0.05) adiposity, whole-body insulin sensitivity, or metabolic profiles in the plasma of obese rats. These results indicate that high concentrations of L-leucine promote glucosamine synthesis and impair NO production by ECs, possibly contributing to an increased risk of cardiovascular disease in diet-induced obese rats.

中文翻译：

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膳食补充 L-亮氨酸可减少大鼠内皮细胞的一氧化氮合成。

这项研究检验了血浆中 L-亮氨酸浓度升高会减少内皮细胞 (EC) 合成一氧化氮 (NO) 并影响肥胖大鼠肥胖的假设。从 4 周龄开始，雄性 Sprague-Dawley 大鼠被喂食基于酪蛋白的低脂 (LF) 或高脂 (HF) 饮食 15 周。此后，LF 和 HF 组的大鼠被随机分配到两个亚组之一（n = 8/亚组），并接受含有 1.02% L-丙氨酸（等氮对照）或 1.5% L-亮氨酸的饮用水 12 周。在补充期的第0周、第6周和第11周测定大鼠的能量消耗。研究结束时，对所有大鼠进行口服葡萄糖耐量测试，然后将其安乐死以收集组织。高频喂养使 EC 中的 NO 合成降低 (P < 0.001) 21%，全身胰岛素敏感性降低 19%，但使 EC 中谷氨酰胺：果糖 6-磷酸转氨酶 (GFAT) 活性增加 (P < 0.001) 42%。口服L-亮氨酸使EC中的NO合成降低（P < 0.05）14％，使EC中的GFAT活性增加（P < 0.05）35％，并使全身胰岛素敏感性降低（P < 0.05）14％饲喂 LF 饮食的大鼠，但对饲喂 HF 饮食的大鼠的这些变量没有影响 (P > 0.05)。L-亮氨酸补充不会影响（P > 0.05）LF-或HF的体重增加、组织块（包括白色脂肪组织、棕色脂肪组织和骨骼肌）或抗氧化能力（以谷胱甘肽/谷胱甘肽二硫化物的比率表示）喂养大鼠，并且肥胖大鼠的肥胖、全身胰岛素敏感性或血浆代谢​​特征并未恶化（P > 0.05）。这些结果表明，高浓度的 L-亮氨酸促进葡萄糖胺合成并损害 EC 的 NO 产生，可能导致饮食诱导的肥胖大鼠患心血管疾病的风险增加。