Regulation of Milk Protein Synthesis by Free and Peptide-Bound Amino Acids in Dairy Cows.

Milk protein (MP) synthesis in the mammary gland of dairy cows is a complex biological process. As the substrates for protein synthesis, amino acids (AAs) are the most important nutrients for milk synthesis. Free AAs (FAAs) are the main precursors of MP synthesis, and their supplies are supplemented by peptide-bound AAs (PBAAs) in the blood. Utilization of AAs in the mammary gland of dairy cows has attracted the great interest of researchers because of the goal of increasing MP yield. Supplying sufficient and balanced AAs is critical to improve MP concentration and yield in dairy cows. Great progress has been made in understanding limiting AAs and their requirements for MP synthesis in dairy cows. This review focuses on the effects of FAA and PBAA supply on MP synthesis and their underlying mechanisms. Advances in our knowledge in the field can help us to develop more accurate models to predict dietary protein requirements for dairy cows MP synthesis, which will ultimately improve the nitrogen utilization efficiency and lactation performance of dairy cows.

Branched chain amino acids alter fatty acid profile in colostrum of sows fed a high fat diet.

BACKGROUND: Branched chain amino acids (BCAAs) are important substrates for milk protein synthesis in the mammary gland, and are tightly related to lipid metabolism. No study has been performed examining the role of BCAAs with high fat diets on milk fat synthesis. This study was designed to investigate the effect of dietary BCAAs on growth performance of piglets, progeny body weight, and milk fat composition in sows fed a high fat diet. Four diets (CON = control diet; HF = high fat diet with 8% soybean oil; HF-MB=HF plus 0.39% BCAAs; HF-HB=HF plus 0.78% BCAAs) were fed to sows from late gestation to weaning. RESULTS: Compared to HF, BCAAs (HF-MB and HF-HB) increased the litter weight (P < 0.05) and overall litter weight gain (P < 0.05) at weaning and increased colostrum fat content by 27.3-35.8% (P < 0.01). Fatty acid profiles between the two doses of BCAAs were similar. Compared with HF, HF-MB tended to decrease the percentage of C18:3n3 (P = 0.063) and increased the percentage of C18:1n9c (P = 0.03). In addition, BCAAs in HF-MB increased the concentration of total fatty acid by 22.1% in colostrum (P = 0.03) but decreased that in serum at parturition by 53.2% (P = 0.027). The fatty acids in colostrum that increased with BCAAs were C15:0, C17:0, C20:3n6, C20:4n6, C20:5n3 and C22:6n3 (P = 0.00~0.04). Colostrum fatty acids of C20:0, C21:0, C22:0, C16:1, C20:1, C18:1n9c also tended to be increased (0.05 < P < 0.1) with BCAAs. The change in sow serum fatty acid profile due to BCAAs was different from that in colostrum. CONCLUSIONS: BCAAs in high fat diet of sows altered the fatty acid composition in colostrum and enhanced litter growth. Our study indicated that BCAAs supplementation can enhance mammary fatty acid uptake and mammary fat synthesis and that supplemental BCAAs and fat in late gestation and lactation diets for sows can improve reproductive performance.

Ellipsoidal magnetite nanoparticles: a new member of the magnetic-vortex nanoparticles family for efficient magnetic hyperthermia.

The development of magnetic iron oxide nanoparticles with novel topological magnetic domain structures, such as the vortex-domain structure, is a promising strategy for improving the application performance of conventional superparamagnetic iron oxides while maintaining their good biocompatibility. Here, we fabricated a new kind of magnetic-vortex nanoparticles, i.e., ellipsoidal magnetite nanoparticles (EMPs), for cancer magnetic hyperthermia. The magnetization configurations and switching behaviours of the EMPs were analyzed by analytical simulations and Lorentz TEM, demonstrating the magnetic vortex structures of both single and coupled EMPs. The EMP treatment of 4T1 cells exposed to an alternating magnetic field (AMF) induced a significant decrease in the cell viability by ∼51.5%, which indicated a much higher cytotoxic effect in comparison with commercial superparamagnetic iron oxides (Resovist, ∼12.0%). In addition, the in vivo high efficacy of 4T1 breast tumor inhibition was also achieved by using EMP-mediated magnetic hyperthermia. Our results not only provide a new type of magnetic-vortex nanoparticles for efficient hyperthermia but also enrich the family of magnetic iron oxide nanoparticles for various biomedical applications.

Methionine Partially Replaced by Methionyl-Methionine Dipeptide Improves Reproductive Performance over Methionine Alone in Methionine-Deficient Mice.

Decreased protein breakdown in pregnant women results in lower concentration of methionine (Met) in plasma, causing pregnancy-related metabolic disturbance. Its dipeptide methionyl-methionine (Met-Met) may exert positive influence in fetal development. This study mainly investigated whether Met-Met can be used as part of free Met to promote reproductive outcomes in mice and the underlying mechanisms. Met-deficient pregnant mice were treated with Met alone or with Met-Met during pregnancy. Daily intraperitoneal injection of 35% dietary Met in pregnant mice was the best dose among the 15⁻45% doses. Embryo development and newborn birth weight were enhanced when 25% of the Met in the 35% Met group was replaced with Met-Met. Met-Met replacement had higher plasma insulin, glucose, and free amino acids (AA) concentrations. Besides, in the placenta, the AA transporter mRNA abundances and peptide transporters (PhT1 and PepT1) protein levels were higher in Met-Met treatment group. Moreover, Met-Met increased 4E-BP1, S6K1 and AKT/mTOR phosphorylation. These results suggest that Met-Met could be used as a partial source of Met to promote reproductive outcomes in Met-restricted pregnant mice, which might be mediated by promoting nutrient availability and activating AKT/mTOR-mediated signaling pathway.

Nutritional and regulatory role of branched-chain amino acids in lactation.

Optimal growth and health of suckling neonates critically depend on milk production by their mothers. In both humans and animals, branched-chain amino acids (BCAA) are not only the major components of milk proteins but are also nitrogenous precursors for the synthesis of glutamate, glutamine, alanine, and aspartate in the mammary gland. These synthetic pathways, which are initiated by BCAA transaminase, contribute to the high abundance of free and peptide-bound glutamate, glutamine, aspartate and asparagine in milk. In mammary epithelial cells, the carbon skeletons of BCAA can be partially oxidized via branched-chain alpha-ketoacid dehydrogenase to provide energy for highly active metabolic processes, including nutrient transport, protein turnover, as well as lipid and lactose syntheses. In addition, results of recent studies indicate that BCAA play regulatory roles in mammary metabolism. For example, leucine can activate the mammalian target of rapamycin cell signaling pathway to enhance protein synthesis in mammary epithelial cells. Dietary supplementation with BCAA may have great potential to enhance milk synthesis by the lactating mammary gland, thereby improving neonatal survival, growth and development.