Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability

Abstract

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids. We analyzed whether reduced urea excretion was a consequence of higher NOx; (nitrite, nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion. There were no differences in plasma nitrate or nitrite. NOx and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithine when compared with controls, whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

The urea cycle of rat white adipose tissue

“…The nding of a complete urea cycle in WAT represents a departure of the concept of liver as the only factual regulator of N disposal. Altered urea cycle in metabolic syndrome 20 and decreased urea production 38 attest a decreasing role of liver in amino acid disposal under conditions of inammation. This fact, so far, remains unexplained in spite of the excess energy and 2-amino N that characterizes dietary-induced metabolic syndrome.…”

Dietary Energy Partition: The Central Role of Glucose

“…However, there is proof of an additional, quantitatively significant, excretion of N as gas through respiration [ 128 , 129 ] that is supplementary to the standard and well-controlled urea excretion. When analyzing in detail N balances in experimental animals, the amount of N ingested is higher than the sum of the N accrued in the body and the N excreted and accounted for [ 130 , 131 ] ( Box 1 ). The proportion of this “nitrogen gap” (assumedly N 2 ) is in the range of 5–15% of all nitrogen ingested and not accrued (i.e., it is actually excreted), and its amount is related to diet and energy status [ 128 , 130 ].…”

“…The proportion of this “nitrogen gap” (assumedly N 2 ) is in the range of 5–15% of all nitrogen ingested and not accrued (i.e., it is actually excreted), and its amount is related to diet and energy status [ 128 , 130 ]. It has been found that this N 2 loss is related to arginine metabolism [ 131 ] ( Figure 7 ).…”

Glomerular Collagen Deposition and Lipocalin-2 Expression Are Early Signs of Renal Injury in Prediabetic Obese Rats

“…However, in cafeteria-diet fed rodents hepatic synthesis of urea significantly decreased due to limited availability of arginine. [24,25] Accordingly, lower serum plasma urea concentration in PRED rats can be due to decreased urea synthesis in the liver, and does not necessarily indicate increased glomerular filtration in PRED compared to CON animals in our study.…”