title: 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.
authors.affiliation: Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Gabriela Fullin Resende
authors.initials: GF
authors.lastname: Teodoro
authors.forename: Daiana
authors.initials: D
authors.lastname: Vianna
authors.forename: Francisco Leonardo
authors.initials: FL
authors.lastname: Torres-Leal
authors.forename: Lucas Carminatti
authors.initials: LC
authors.lastname: Pantaleão
authors.forename: Emídio Marques
authors.initials: EM
authors.lastname: Matos-Neto
authors.forename: Jose
authors.initials: J
authors.lastname: Donato
authors.forename: Julio
authors.initials: J
authors.lastname: Tirapegui
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D004044:Dietary Proteins / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005317:Fetal Growth Retardation / Q000178:diet therapy* / Q000517:prevention & control*; D007930:Leucine / Q000494:pharmacology*; D008099:Liver / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D004044:Dietary Proteins; D011506:Proteins; D012709:Serum Albumin; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D007930:Leucine