Dietary supplementation with L-leucine reduces nitric oxide synthesis by endothelial cells of rats.

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 ( = 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 ( < 0.001) NO synthesis in ECs by 21% and whole-body insulin sensitivity by 19% but increased ( < 0.001) glutamine:fructose-6-phosphate transaminase (GFAT) activity in ECs by 42%. Oral administration of L-leucine decreased ( < 0.05) NO synthesis in ECs by 14%, increased ( < 0.05) GFAT activity in ECs by 35%, and reduced ( < 0.05) whole-body insulin sensitivity by 14% in rats fed the LF diet but had no effect ( > 0.05) on these variables in rats fed the HF diet. L-Leucine supplementation did not affect ( > 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 ( > 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.