Glycinergic Signaling in Macrophages and Its Application in Macrophage-Associated Diseases.

Accumulating evidences support that amino acids direct the fate decision of immune cells. Glycine is a simple structural amino acid acting as an inhibitory neurotransmitter. Besides, glycine receptors as well as glycine transporters are found in macrophages, indicating that glycine alters the functions of macrophages besides as an inhibitory neurotransmitter. Mechanistically, glycine shapes macrophage polarization via cellular signaling pathways (e.g., NF-κB, NRF2, and Akt) and microRNAs. Moreover, glycine has beneficial effects in preventing and/or treating macrophage-associated diseases such as colitis, NAFLD and ischemia-reperfusion injury. Collectively, this review highlights the conceivable role of glycinergic signaling for macrophage polarization and indicates the potential application of glycine supplementation as an adjuvant therapy in macrophage-associated diseases.

Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4/NOD/NF-κB signaling pathway in weaned piglets with intrauterine growth retardation.

The aim of present study was to evaluate whether diets supplemented with dihydroartemisinin (DHA) could alleviate intestinal inflammatory injury in weaned piglets with intrauterine growth retardation (IUGR). Twelve normal birth weight (NBW) piglets and 12 piglets with IUGR were fed a basal diet (NBW-CON and IUCR-CON groups), and another 12 piglets with IUGR were fed the basal diet supplemented with DHA at 80 mg/kg (IUGR-DHA group) from 21 to 49 d of age. At 49 d of age, 8 piglets with similar body weight in each group were sacrificed. The jejunal and ileal samples were collected for further analysis. The results showed that IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated transmembrane toll-like receptor 4 (TLR4)/nucleotide-binding and oligomerization domain (NOD)/nuclear factor-κB (NF-κB) signaling pathway. Dihydroartemisinin inclusion ameliorated intestinal morphology, indicated by increased villus height, villus height-to-crypt depth ratio, villus surface area and decreased villus width of piglets with IUGR (P < 0.05). Compared with NBW piglets, IUGR piglets supplemented with DHA exhibited higher apoptosis index and caspase-3 expression, and lower proliferation index and proliferating cell nuclear antigen expression in the intestine (P < 0.05). Dihydroartemisinin supplementation attenuated the intestinal inflammation of piglets with IUGR, indicated by increased concentrations of intestinal inflammatory cytokines and lipopolysaccharides (P < 0.05). In addition, DHA supplementation down-regulated the related mRNA expressions of TLR4/NOD/NF-κB signaling pathway and upregulated mRNA expressions of negative regulators of TLR4 and NOD signaling pathway in the intestine of piglets with IUGR (P < 0.05). Piglets in the IUGR-DHA group showed lower protein expressions of TLR4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and higher protein expression of cytoplasmic pNF-κB in the intestine than those in the IUGR-CON group (P < 0.05). In conclusion, DHA supplementation could improve intestinal morphology, regulate enterocyte proliferation and apoptosis, and alleviate intestinal inflammation through TLR4/NOD/NF-κB signaling pathway in weaned piglets with IUGR.

Effect of Vitamin E Supplementation on Deposition and Gene Expression Profiling of Abdominal Fat in Broiler Chickens.

The aim of this study was to study the regulation of abdominal fat deposition by DL-α-tocopherol acetate (vitamin E) in broilers. Diets supplemented with 50 IU vitamin E significantly diminished abdominal fat deposition in broilers at day 35. Transcriptome sequencing results for abdominal fat tissues of the control (FC) and 50 IU vitamin E-supplemented (FT) groups identified 602 differentially expressed genes (DEGs), which were enriched in cellular process, cell and cell part, and binding Gene Ontology terms. Pathway functional analysis revealed that the DEGs were enriched in 42 metabolic pathways. Notably, the most enriched pathway, fatty acid biosynthesis, was found to play a key role in lipid metabolism. Further, the key regulators of lipid metabolism, including fatty acid synthase, acetyl-CoA carboxylase alpha, and acyl-CoA synthetase long-chain family member 1, demonstrated decreased expression following vitamin E supplementation. Herein, we have identified pathways and genes regulated by vitamin E, thereby providing novel insights into the nutrients regulating abdominal fat deposition in broilers.

Effects of dietary dihydroartemisinin supplementation on growth performance, hepatic inflammation, and lipid metabolism in weaned piglets with intrauterine growth retardation.

The aims of this study were to investigate the effects of dietary supplementation with dihydroartemisinin (DHA) on growth performance, hepatic inflammation, and lipid metabolism in intrauterine growth retardation (IUGR)-affected weaned piglets. Eight piglets with normal birth weight (NBW) and 16 IUGR-affected piglets were selected and fed either a basal diet (NBW and IUGR groups) or the basal diet supplemented with 80 mg/kg DHA (IUGR-DHA group) from 21 to 49 day of age. Blood and liver samples were collected on day 49. DHA supplementation significantly alleviated the compromised growth performance and liver damage in IUGR-affected piglets. Additionally, DHA supplementation decreased the activities of alanine aminotransferase and aspartate aminotransferase, as well as the serum levels of non-esterified fatty acids (NEFA), very-low-density lipoprotein, and total cholesterol. In the liver, the concentrations of interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, triglycerides, and NEFA were decreased. Fatty acid synthesis was decreased by DHA supplementation, whereas the activities of lipoprotein lipase, hepatic lipase, and total lipase were increased. Dietary DHA supplementation led to upregulation of the expression of AMPK/SIRT1 signaling pathway-related genes, whereas that of inflammatory factor-related genes were downregulated. In conclusion, dietary inclusion of 80 mg/kg DHA can alleviate IUGR-induced impairments in piglets.

Dietary Curcumin Supplementation Increases Antioxidant Capacity, Upregulates Nrf2 and Hmox1 Levels in the Liver of Piglet Model with Intrauterine Growth Retardation.

Curcumin has improved effects on antioxidant capacity via multiple mechanisms. Intrauterine growth retardation (IUGR) has had adverse influences on human health. IUGR is always associated with elevated oxidative stress and deficiencies in antioxidant defense. Therefore, we chose IUGR piglets as a model to investigate the effects of IUGR on antioxidant capacity of newborn and weaned piglets and determine how these alterations were regulated after supplementation with curcumin in weaned IUGR piglets. In experiment 1, eight normal-birth-weight (NBW) and eight IUGR newborn piglets were selected to determine the effect of IUGR on the antioxidant capacity of neonatal piglets. In experiment 2, thirty-two weaned piglets from four experimental groups: NBW, NC (curcumin supplementation), IUGR, IC (curcumin supplementation) were selected. The results showed that both IUGR newborn and weaned piglets exhibited oxidative damage and lower antioxidant enzymes activities in the liver compared with the NBW piglets. Dietary curcumin supplementation increased body-weight gain, feed intake, activities of antioxidant enzymes, and the expressions of nuclear factor, erythroid 2-like 2 (Nrf2) and heme oxygenase-1 (Hmox1) proteins in the liver of weaned piglets with IUGR. In conclusion, IUGR decreased the antioxidant capacity of newborn and weaned piglets. Curcumin could efficiently improve the growth, increase hepatic antioxidant capacity, and upregulate Nrf2 and Hmox1 levels in the liver of IUGR weaned piglets.

Curcumin and Resveratrol Regulate Intestinal Bacteria and Alleviate Intestinal Inflammation in Weaned Piglets.

Human infants or piglets are vulnerable to intestinal microbe-caused disorders and inflammation due to their rapidly changing gut microbiota and immaturity of their immune systems at weaning. Resveratrol and curcumin have significant anti-inflammatory, bacteria-regulating and immune-promoting effects. The purpose of this study was to investigate whether dietary supplementation with resveratrol and curcumin can change the intestinal microbiota and alleviate intestinal inflammation induced by weaning in piglets. One hundred eighty piglets weaned at 21 ± 2 d were fed a control diet (CON group) or supplemented diet (300 mg/kg of antibiotics, ANT group; 300 mg/kg of resveratrol and curcumin, respectively, HRC group; 100 mg/kg of resveratrol and curcumin, respectively, LRC group; 300 mg/kg of resveratrol, RES group; 300 mg/kg of curcumin, CUR group) for 28 days. The results showed that compared with the CON group, curcumin alone and antibiotics decreased the copy numbers of Escherichia coli. Both curcumin and resveratrol down-regulated the level of Toll-like-receptor 4 mRNA and protein expression in the intestine to inhibit the release of critical inflammation molecules (interleukin-1ß, tumor necrosis factor-α), and increase the secretion of immunoglobulin. Our results suggested that curcumin and resveratrol can regulate weaned piglet gut microbiota, down-regulate the TLR4 signaling pathway, alleviate intestinal inflammation, and ultimately increase intestinal immune function.