PMID- 28237591 OWN - NLM STAT- MEDLINE DCOM- 20170522 LR - 20170522 IS - 1525-3198 (Electronic) IS - 0022-0302 (Linking) VI - 100 IP - 5 DP - 2017 May TI - Methionine, leucine, isoleucine, or threonine effects on mammary cell signaling and pup growth in lactating mice. PG - 4038-4050 LID - S0022-0302(17)30165-0 [pii] LID - 10.3168/jds.2016-11973 [doi] AB - Two studies were undertaken to assess the effects of individual essential AA supplementation of a protein-deficient diet on lactational performance in mice using litter growth rates as a response variable. The first study was designed to establish a dietary protein response curve, and the second to determine the effects of Leu, Ile, Met, and Thr supplementation of a protein-deficient diet on lactational performance. In both studies, dams were fed test diets from parturition through d 17 of lactation, when the studies ended. Mammary tissue was collected on d 17 from mice on the second experiment and analyzed for mammalian target of rapamycin (mTOR) pathway signaling. Supplementation with Ile, Leu, or Met independently increased litter weight gain by 11, 9, and 10%, respectively, as compared with the protein-deficient diet. These responses were supported by independent phosphorylation responses for mTOR and eIF4E binding protein 1 (4eBP1). Supplementation of Ile, Leu, and Met increased phosphorylation of mTOR by 55, 34, and 47%, respectively, as compared with the protein-deficient diet. Phosphorylation of 4eBP1 increased in response to Ile and Met supplementation by 60 and 40%, respectively. Supplementation of Ile and Met increased phosphorylation of Akt/protein kinase B (Akt) by 41 and 59%, respectively. This work demonstrated that milk production responds nonlinearly to protein supply, and milk production and the mTOR pathway responded independently to supplementation of individual AA. The former demonstrates that a linear breakpoint model is an inappropriate description of the responses, and the latter demonstrates that no single factor limits AA for lactation. Incorporation of a multiple-limiting AA concept and nonlinear responses into milk protein response models will help improve milk yield predictions and allow derivation of diets that will increase postabsorptive N efficiency and reduce N excretion by lactating animals. CI - Copyright (c) 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved. FAU - Liu, G M AU - Liu GM AD - Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, P. R. China. FAU - Hanigan, M D AU - Hanigan MD AD - Department of Dairy Science, Virginia Tech, Blacksburg 24061. FAU - Lin, X Y AU - Lin XY AD - Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, P. R. China. FAU - Zhao, K AU - Zhao K AD - Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, P. R. China. FAU - Jiang, F G AU - Jiang FG AD - Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, P. R. China. FAU - White, R R AU - White RR AD - Department of Dairy Science, Virginia Tech, Blacksburg 24061. FAU - Wang, Y AU - Wang Y AD - Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, P. R. China. FAU - Hu, Z Y AU - Hu ZY AD - Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, P. R. China. FAU - Wang, Z H AU - Wang ZH AD - Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, P. R. China. Electronic address: zhwang@sdau.edu.cn. LA - eng PT - Journal Article DEP - 20170223 PL - United States TA - J Dairy Sci JT - Journal of dairy science JID - 2985126R RN - 0 (Milk Proteins) RN - 04Y7590D77 (Isoleucine) RN - 2ZD004190S (Threonine) RN - AE28F7PNPL (Methionine) RN - GMW67QNF9C (Leucine) SB - IM MH - Animals MH - Diet MH - Isoleucine/*pharmacology MH - Lactation MH - Leucine/*pharmacology MH - Methionine/metabolism MH - Mice MH - Milk/metabolism MH - Milk Proteins/pharmacology MH - Threonine/pharmacology OTO - NOTNLM OT - cell signaling OT - litter growth rates OT - mice OT - single amino acid EDAT- 2017/02/27 06:00 MHDA- 2017/05/23 06:00 CRDT- 2017/02/27 06:00 PHST- 2016/09/07 00:00 [received] PHST- 2017/01/03 00:00 [accepted] PHST- 2017/02/27 06:00 [pubmed] PHST- 2017/05/23 06:00 [medline] PHST- 2017/02/27 06:00 [entrez] AID - S0022-0302(17)30165-0 [pii] AID - 10.3168/jds.2016-11973 [doi] PST - ppublish SO - J Dairy Sci. 2017 May;100(5):4038-4050. doi: 10.3168/jds.2016-11973. Epub 2017 Feb 23.