Leucine Is Essential for Attenuating Fetal Growth Restriction Caused by a Protein-Restricted Diet in Rats

Abstract

Certain amino acids, such as leucine (Leu) are not only substrates for protein synthesis but also are important regulators of protein metabolism. Moreover, it is known that alterations in intrauterine growth favor the development of chronic diseases in adulthood. Therefore, we investigated the role of Leu in combination with other BCAA on effects that are induced by maternal protein restriction on fetal growth. Wistar rats were divided into 4 groups according to the diet provided during pregnancy: control (C; 20% casein); V+I [5% casein + 2% L-valine (Val) + 2% L-isoleucine (Ile)]; KYT [5% casein + 1.8% L-lysine (Lys) + 1.2% L-tyrosine (Tyr) + 1% L-threonine (Thr)]; and BCAA (5% casein + 1.8% L-Leu + 1.2% L-Val + 1% L-Ile). Maternal protein restriction reduced the growth and organ weight of the offspring of dams receiving the V+I and KYT diets compared with the C group. Supplementation with BCAA reversed this growth deficit, minimizing the difference or restoring the mass of organs and carcass fat, the liver and muscle protein, and the RNA concentrations compared with newborns in the C group (P < 0.05). These effects could be explained by the activation of the mTOR signaling pathway, because phosphorylation of 4E-BP1 in the liver of offspring of the BCAA group was greater than that in the C, V+I, and KYT groups. The present results identify a critical role for Leu in association with other BCAA in the activation of the mTOR signaling pathway for the control of altered intrauterine growth induced by a maternal low-protein diet.

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons

“…In support of this idea, decreased fetomaternal enrichment ratios of leucine have been reported to be correlated with the severity of IUGR in the human at term [33, 34]. Furthermore, leucine supplementation has been shown to prevent fetal growth restriction in rats fed a low protein diet [35]. …”

Dietary melatonin supplementation alters uteroplacental amino acid flux during intrauterine growth restriction in ewes

“…Moreover, supplementation of BCAA to dams on a protein deficient diet can restore fetal growth and minimize the decreases in fetal organ mass and carcass fat, which is associated with increased mTOR signaling (Teodoro et al, 2012). For the current study, a decreased fetal uptake of BCAA was observed in fetuses from nutrient restricted ewes, while maternal melatonin supplementation Table 3 Glucose concentrations, maternal AV difference, fetal va difference, uterine uptake, fetal uptake, and uteroplacental uptake of glucose and fetal concentrations of liver glycogen and total liver glycogen at day 130 of gestation from ewes supplemented with 5 mg of MEL or CON and provided 100% (ADQ diet) or 60% (RES diet) of nutrient recommendations beginning on day 50 of gestation Ovine uteroplacental flux of nutrients improved BCAA uptake.…”

Nutritional epigenetics with a focus on amino acids: implications for the development and treatment of metabolic syndrome

“…Changes in intracellular protein turnover affect concentrations of proteins involved in epigenetic regulation of gene expression. Thus, there is evidence that leucine, in combination with isoleucine and valine to ensure their balance in diets, helps to improve intrauterine growth brought about by maternal protein restriction via activating the mTOR signaling pathway [73,79]. Conversely, leucine deprivation elevates phosphorylated levels of IGFBP-1, which in turn suppresses IGF-I-stimulated cell proliferation and hence results in fetal growth restriction [80].…”