Taurine alleviates oxidative stress in porcine mammary epithelial cells by stimulating the Nrf2-MAPK signaling pathway.

The high incidence of oxidative stress in sows during late gestation and lactation affects mammary gland health, milk yield, and milk quality. Recently, we found that supplementing maternal diets with 1% taurine improved antioxidant capability and enhanced growth performance in offspring; however, the mechanisms underlying these are unknown. This study aimed to investigate the cytoprotective effects and the mechanism of taurine in mitigating oxidative stress in porcine mammary epithelial cells (PMECs). PMECs were pretreated with 0-2.0 mM taurine for 12 h and then subjected to oxidative injury with 500 µM hydrogen peroxide (H2O2). Pretreatment with taurine attenuated decreased cell viability, enhanced superoxide dismutase, and reduced the intracellular reactive oxygen species accumulation after H2O2 exposure. Taurine also prevented H2O2-induced endoplasmic reticulum stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) was essential to the cytoprotective effects of taurine on PMECs, as Nrf2 knockdown significantly inhibited taurine-induced cytoprotection against oxidative stress. Moreover, we confirmed that Nrf2 induction by taurine was mediated through the inactivation of the p38/MAPK pathway. Overall, taurine supplementation has beneficial effects on redox balance regulation and may protect against oxidative stress in lactating animals.

Molecular mechanism of valine and its metabolite in improving triglyceride synthesis of porcine intestinal epithelial cells.

An insufficient energy supply to intestinal epithelial cells decreases production performance in weaned piglets. Triglycerides are the main energy source for intestinal epithelial cells in piglets. The present study aimed to investigate the effects and mechanisms of valine supplementation on triglyceride synthesis in porcine intestinal epithelial (IPEC-J2) cells. Valine supplementation in the medium significantly increased the content of triglycerides, fat droplets, and long-chain fatty acids (C17:0, C18:0, C20:0, C18:1, C20:1, and C22:1) (P < 0.05). Valine metabolite (3-hydroxyisobutyrate [3-HIB]) concentration increased significantly in the valine-supplemented group (P < 0.05). Silencing of the 3-HIB synthase enzyme 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) in IPEC-J2 cells significantly reduced the triglyceride concentration and lipid droplet synthesis. Further studies found that 3-HIB supplementation in the medium significantly increased the concentration of triglycerides, lipid droplets, and unsaturated fatty acids (C16:1, C18:1, C18:2, C18:3, C20:3, C20:4, and C20:5) (P < 0.05) by upregulating the expression of proteins involved in fatty acid transport (CD36) and fatty acid binding protein 3 (FABP3) or triglyceride synthesis (DGAT1) (P < 0.05), indicating that 3-HIB mediates valine-enhanced triglyceride synthesis in IPEC-J2 cells. In conclusion, our results demonstrated that valine enhanced triglyceride synthesis in IPEC-J2 cells via increasing the 3-HIB concentration, which may promote fatty acid transport via upregulation of proteins related to fatty acid transporter. These findings provide new insights into the mechanisms through which valine participates in lipid metabolism.

Valine supplementation during late pregnancy in gilts increases colostral protein synthesis through stimulating mTOR signaling pathway in mammary cells.

Mammary gland development during late pregnancy in sows is a major factor affecting the composition of colostrum and milk and the pre-weaning growth of piglets, while valine is essential for protein and nitrogen metabolism in mammary gland of sow. However, the effects of valine and its underlying mechanism on mammary gland development during late pregnancy are still unclear. Here, we hypothesized that dosage of dietary valine during late pregnancy will affect protein synthesis of colostrum in gilts. The results showed that supplementation of valine during late pregnancy significantly increased content of protein (P < 0.01), fat (P = 0.02) and solids-non-fat (P = 0.04) in colostrum. Our in vitro study also confirmed that valine supplementation increased protein synthesis and cell proliferation in porcine mammary epithelial cells (PMEC). Furthermore, these changes were associated with elevated phosphorylation levels of mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase (S6) and eukaryotic initiation factor 4E-binding protein-1 (4EBP1) in valine-supplemented cells, which could be effectively blocked by the antagonists of mTOR. These findings indicated that valine enhanced mammary gland development and protein synthesis in colostrum via the mTOR signaling pathway. These results, using an in vivo and in vitro model, helped to understand the beneficial effects of dietary valine supplementation on gilts.

Effects of Dietary Taurine Supplementation to Gilts during Late Gestation and Lactation on Offspring Growth and Oxidative Stress.

Birth is one of the most important events of animal production agriculture, as newborns are abruptly forced to adapt to environmental and nutritional disruptions that can lead to oxidative damage and delay in growth. Taurine (Tau) is an important regulator of oxidative stress and possesses growth-enhancing properties. In the present study, we investigated the effects of dietary Tau supplementation in gilts during late gestation and lactation on the growth performance of piglets by assessing intestinal morphology and barrier function, and oxidative stress status. Sixteen gilts were randomly allocated to the Con (basal diet) and Tau (basal diet with 1% Tau) groups from 75 d of gestation to weaning. Maternal dietary Tau supplementation significantly increased weaning weight and average daily gain weight in piglets. Piglets in the Tau group had higher villus height and villus height-to-crypt depth ratio (VCR), ZO-1 protein expression, and secretory immunoglobulin A (sIgA) content in the jejunum. Meanwhile, Tau bebeficial affected the milk quality of gilts, as indicated by decreased malondialdehyde (MDA) concentration and increased total superoxide dismutase (T-SOD), total antioxidative capability (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activity. Furthermore, Tau supplementation increased T-SOD activity in plasma and SOD2 protein expression in the jejunum in the piglets. In conclusion, this study provides evidence that dietary Tau supplementation to gilts improves growth performance in piglets, owing to improved intestinal morphology and barrier function, as well as inhibition of oxidative stress.

Valine increases milk fat synthesis in mammary gland of gilts through stimulating AKT/MTOR/SREBP1 pathway†.

Lactating mammary glands are among the most active lipogenic organs and provide a large percentage of bioactive lipids and calories for infant growth. The branched-chain amino acid (BCAA) valine is known to modulate fatty acids synthesis in adipose tissue; however, its effects on fat metabolism and the underlying mechanisms in mammary glands remain to be determined. Valine supplementation during late pregnancy significantly increased the contents of total milk fat, triglyceride, sphingomyelin, and polyunsaturated fatty acids in the colostrum of gilts. Further study in porcine mammary epithelial cells (PMECs) confirmed that valine upregulated the phosphorylation levels of AKT-activated MTOR and subsequently induced the nuclear accumulation of sterol regulatory element binding protein 1 (SREBP1), thus increasing the expression of proteins related to fatty acids synthesis and intracellular triacylglycerol content. Inhibition of AKT/MTOR signaling or silencing of SREBP1 in PMECs downregulates the expression of proteins related to fatty acids synthesis and intracellular triacylglycerol content. Our findings indicated that valine enhanced milk fat synthesis of colostrum in porcine mammary glands via the AKT/MTOR/SREBP1 signaling pathway.