Effects of branched-chain amino acid supplementation in dams fed a low-protein diet on protein metabolism of dams and liver development of offspring

Abstract

Maternal nutritional environment is closely related to the growth of offspring. Maternal low-protein (LP) diet has been reported to cause catabolic state of dams and restrict fetal liver development, resulting in adult metabolic disease. Branched-chain amino acid (BCAA) can directly activate mTOR pathway and promote protein synthesis especially by leucine. Therefore, this study investigated whether maternal BCAA supplementation would alter maternal protein metabolism and liver growth of weaned offspring. Female CD-1 mice were fed a diet containing normal protein (NP, 20% casein), low protein (LP, 10% casein), LP with 2.1% BCAA (BCAA) or LP with 2.1% alanine (Ala) for two weeks before mating and throughout pregnancy and lactation. Dams and offspring were analyzed at postpartum (PP) day 21. To see whether maternal LP model was properly induced and maintained during pregnancy, dams and offspring were additionally analyzed at PP2 or 3. There were no significant differences by BCAA supplementation in organ weights and serum parameters in dams and offspring at PP2 or 3. As compared to LP group, BCAA and Ala group of PP21 dams showed a significantly higher serum albumin, hepatic total protein and S6 protein levels which were significantly lower in LP group than in NP group. Moreover, as compared to NP group, BCAA and Ala group of PP21 dams showed the significantly higher leptin levels, which had a significant correlation with total liver protein levels, suggesting the relation between increased leptin and hepatic protein synthesis. PD21 offspring from dams fed an LP diet represented the features of retarded liver development, including higher proliferating cell nuclear antigen levels, lower levels of area of hepatic sinusoids, hepatocyte nuclear factor 4α which is core hepatic growth factor and low-density lipoprotein receptor which located on liver sinusoids. Both in BCAA-O and Ala-O group, area of sinusoids was significantly increased than in LP-O group. In conclusion, maternal BCAA supplementation from pre-pregnancy to lactation did not show specific effects on maternal protein metabolism and liver development of weaned offspring which were restricted by maternal LP diet. Improved indicators observed both in BCAA and Ala group of dams and offspring may have been induced by increased nitrogen of amino acid supplementation on LP diet, not by BCAA.