Sung-Ling Yeh

Effects of Fish Oil in Parenteral Nutrition

OBJECTIVEnFish oil is a rich source of omega-3 fatty acids (FAs), especially eicosapentaenoic acid and docosahexaenoic acid. The existing data suggest that eicosapentaenoic acid and docosahexaenoic acid are the active agents in fish oil. A number of clinical trials have shown that dietary fish oil supplementation has antiatherogenic properties and immunomodulation effects. Fish oils are not used widely in parenteral nutrition because fish oil emulsions have not been commercially available until very recently. Studies concerning the use of fish oil in parenteral route are rare.nnnMETHODSnWe reviewed the effect of parenteral fish oil infusion on lipid metabolism and immune response in normal and disease conditions.nnnRESULTSnStudies showed that the main effects of parenteral infusion of fish oil are: 1) incorporation of omega-3 FAs into cellular membranes of many cell populations that consequently influence the disease process of some disease conditions, 2) an effect on eicosanoid metabolism leading to a decrease in platelet aggregation and thrombosis, 3) amelioration of the severity of diet-induced hepatic steatosis, 4) less accumulation of lipid peroxidation products in liver tissue, and 5) immunomodulation effects and therapeutic benefits in animal disease models or various disease conditions of humans. Most of these studies suggested that parenteral infusion of omega-3 FAs have clinical beneficial effects comparable to those of dietary administration. However, different effects of omega-3 and omega-6 FAs in some situations has been reported. For example, plasma triacylglycerol levels were not lowered after fish oil infusion in normal or diabetic rats when compared with those of safflower oil or soybean oil infusion. The reason for the difference remain unclear.nnnCONCLUSIONnThe metabolic and immunologic effects of parenteral use of omega-3 FAs requires further evaluation, especially in some disease conditions.

Glutamine modulates lipopolysaccharide-induced activation of NF-κB via the Akt/mTOR pathway in lung epithelial cells

Lung epithelial cells are important barriers in the respiratory system that provoke inflammatory responses through nuclear factor (NF)-κB activation to prevent pathogens from invading the body. Lipopolysaccharide (LPS) is a common pathogen-associated stimulus that activates IκB kinase (IKK) to regulate NF-κB-mediated inflammation through modulating nuclear translocation and phosphorylation of NF-κB. Previously, it was shown that Akt and the mammalian target of rapamycin (mTOR) are involved in the phosphorylation of IKK to activate NF-κB. Herein, we demonstrate that glutamine (GLN) modulated LPS-induced activation of NF-κB through the Akt/mTOR/IKK pathway in BEAS-2B cells. BEAS-2B cells in submerged culture were placed in medium containing different concentrations of GLN (0, 0.5, 1, and 2.5 mM) with 1 μg/ml LPS. Results showed that GLN deprivation induced phosphorylation of Akt/mTOR/IKK signaling, increased levels of NF-κB nuclear translocation and phosphorylated NF-κB, and upregulated NF-κB-dependent transcriptional activity, which was suppressed by GLN administration. Expressions of NF-κB-targeted genes were also reduced by supplemental GLN. GLN administration improved cell viability, whereas 0.5 mM GLN had a greater extent of inhibition on the Akt/mTOR/IKK/NF-κB signaling cascade. The inhibitory effects of GLN on NF-κB activation were also observed in cells cultured under air-liquid interface condition. These results indicate that GLN deprivation increased LPS-induced NF-κB activation and transcriptional activity, which was reversed by GLN administration. The findings provide potential mechanisms of GLNs modulation of LPS-induced NF-κB activation in lung epithelial cells and imply that maintaining a physiological concentration of GLN is essential in preventing LPS-induced lung inflammation.

Effects of ω-3 fatty acids on inflammatory mediators and splenocyte cytokine mRNA expressions in rats with polymicrobial sepsis

OBJECTIVESnMany studies have shown that omega-3 fatty acids (FAs) have immunomodulatory effects. However, the influence of omega-3 FAs on septic conditions is not certain. This study examined the effect of fish oil (FO)-enriched diets before and/or omega-3 FA-containing total parenteral nutrition (TPN) after sepsis on the distribution of T-lymphocyte subpopulations and splenocyte cytokine mRNA expressions in rats with polymicrobial sepsis.nnnMETHODSnRats were assigned to a control group and four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet, and groups 3 and 4 had 20% soybean oil replaced by FO. After feeding the diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP) in the experimental groups, whereas sham operation was performed on the control group. TPN was maintained for 3 d after CLP or sham operation. The control group and groups 1 and 3 were infused with conventional TPN, whereas the TPN solution of groups 2 and 4 was supplemented with FO. All rats were sacrificed 3 d after the operation to examine their immune responses.nnnRESULTSnMessenger RNA expressions of interleukin-2 and tumor necrosis factor-alpha in splenocytes were higher in groups 3 and 4 than in the control group and group 1. Interleukin-10 mRNA expression in group 3 was higher than in the control group and group 2. Blood CD4 percentage and CD4/CD8 ratio in group 1 were significantly lower, whereas no differences were observed in FO-supplemented groups compared with the control group.nnnCONCLUSIONnFO administration before and/or after CLP maintained blood T-lymphocyte subpopulations and modulated T-helper type 1 and 2 cytokine mRNA expressions in rats with polymicrobial sepsis.

Dietary arginine enhances adhesion molecule and T helper 2 cytokine expression in mice with gut-derived sepsis

ABSTRACT This study investigated the effects of arginine (Arg) on cellular adhesion molecules and intracellular Th1/Th2 cytokine expressions in mice with polymicrobial sepsis. Myeloperoxidase activity in organs was also analyzed to identify the extent of tissue injury resulting from neutrophil infiltration. Mice were randomly assigned to a normal group (NC), a control group, or an Arg group. The NC group was fed a standard chow diet. The control group was fed a common semipurified diet, and in the Arg group, part of the casein was replaced by Arg, which provided 2% of the total calories. After 3 weeks, sepsis was induced by cecal ligation and puncture (CLP) in the control and Arg groups. Mice in the experimental groups were sacrificed at 0, 6, 12, and 24 h after CLP, whereas mice in the NC group were sacrificed when the CLP was performed. Blood and organ samples were immediately collected for further analysis. Results showed that compared with the control group, plasma intracellular adhesion molecule-1 levels were significantly higher in the Arg group 12 and 24 h after CLP. Lymphocyte interferon-&ggr; expression in the Arg groups was significantly lower, whereas interleukin (IL)-4 expression was higher than the control group at various time points after CLP. The expression of lymphocyte CD11a/CD18 was significantly higher in the Arg group 6, 12, and 24 h after CLP than those of the corresponding control group and the NC group. PMN expressions of CD11b/CD18 in the Arg groups were higher than those in the control group at 12 and 24 h after CLP. The Arg group had higher IL-6 levels at 6 and 12 h in the kidney and intestine and 12 h in the lung after CLP. Higher myeloperoxidase activities were observed in the Arg groups at 24 h after CLP than those in the control group in various organs. These findings suggest that pretreatment with an Arg-supplemented diet enhances adhesion molecule and inflammatory cytokine expression during sepsis, which may aggravate the inflammatory reaction and increase neutrophil infiltration into tissues. In addition, Arg supplementation reduced intracellular interferon-&ggr; and enhanced IL-4 expression. This change may promote the Th2-type response and suppress the cellular immune response in gut-derived sepsis.

Effect of dietary fish oil supplementation on cellular adhesion molecule expression and tissue myeloperoxidase activity in diabetic mice with sepsis.

This study investigated the effect of n-3 fatty acids on adhesion molecules and tissue myeloperoxidase (MPO) activity in diabetic mice with sepsis. Diabetes was induced by a streptozotocin injection. Mice with blood glucose levels exceeding 2000 mg/l were considered diabetic. Diabetic mice were assigned to two groups with a medium-fat (10 %, w/w) diet either provided by soyabean oil (SO, n 30) or fish oil (FO, n 30). n-3 fatty acids provided 4.3 % of the total energy and the n-3/n-6 fatty acid ratio was 1:2 in the FO diet. After feeding the respective diet for 3 weeks, all mice had sepsis induced by caecal ligation and puncture (CLP) and were killed at 0, 6 or 24 h after CLP, with ten mice at each time-point. The result showed that compared with the SO group, FO group had lower PGE2 and TNF-alpha levels in peritoneal lavage fluid after CLP. Lymphocyte CD11a/CD18 expressions were higher at 6 h, whereas the percentage was lower at 24 h in the SO group than in the FO group. Neutrophil CD11b/CD18 expressions were significantly higher in the SO group than in the FO group at 0 h. The FO group had lower organ MPO activities at various time-points after CLP when compared with those of the SO group. The present findings suggest that compared with the diabetic mice fed SO, a low-dose n-3 fatty acid supplementation may attenuate leucocyte adhesion and infiltration into tissues in diabetic mice complicated with sepsis.

Dietary glutamine supplementation enhances endothelial progenitor cell mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia.

Diabetes is a metabolic disorder with increased risk of vascular diseases. Tissue ischemia may occur with diabetic vascular complications. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. This study investigated the effects of oral glutamine (GLN) supplementation on circulating EPC mobilization and expression of tissue EPC-releasing markers in diabetic mice subjected to limb ischemia. Diabetes was induced by a daily intraperitoneal injection of streptozotocin for 5 days. Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One of the nonischemic and 3 ischemic groups were fed the control diet, while the remaining 4 groups received diets with identical components except that part of the casein was replaced by GLN. The respective diets were fed to the mice for 3 weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or 21 days after ischemia. Their blood and ischemic muscle tissues were collected for further analyses. Results showed that plasma matrix metallopeptidase (MMP)-9 and the circulating EPC percentage increased after limb ischemia in a diabetic condition. Compared to groups without GLN, GLN supplementation up-regulated plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1, hypoxia-inducible factor-1 and vascular endothelial growth factor gene expression. The CD31-immunoreactive intensities were also higher in the ischemic limb. These findings suggest that GLN supplementation enhanced circulating EPC mobilization that may promote endothelium repair at ischemic tissue in diabetic mice subjected to limb ischemia.

Effects of fish oil-based lipid emulsion on inflammation and kidney injury in mice subjected to unilateral hind limb ischemia/reperfusion

HighlightsThis study evaluated the impact of fish oil (FO) emulsion on muscle and renal damage in a model of limb ischemia/reperfusion.Supplementing FO emulsion either before or after IR injury alleviated IR‐induced inflammatory gene expression in muscle and kidney tissues.FO given after IR injury limited muscle leukocytic infiltration, can better downregulate the inflammation seen in IR‐induced remote kidney injury and improved renal histology. Abstract This study investigated the effects of a fish oil‐based lipid emulsion (FO) on local skeletal muscle and remote renal damage at 72 h post‐reperfusion in a murine model of hind limb ischemia‐reperfusion (IR) injury. Mice were assigned to 1 sham group and 3 IR groups. The IR groups were treated daily with either saline or FO from 3 days prior to limb ischemia till 3 days after reperfusion. Limb IR was induced by applying a 4.5‐oz orthodontic rubber band above the left greater trochanter for 120 min followed by band‐released reperfusion for 72 h. Mice were then sacrificed to harvest blood, muscle, and kidney for analysis. The results showed that IR injury led to upregulation of pro‐inflammatory monocytes in blood, infiltration of leukocytes into injured muscle, and over‐expression of pro‐inflammatory genes in muscle and kidney tissues. Supplementing FO either before or after IR injury alleviated IR‐induced inflammatory gene expressions in muscle and kidney tissues. Furthermore, FO given after IR injury reduced circulating pro‐inflammatory monocytes, limited muscle leukocytic infiltration, and improved renal histology. These results suggest that FO may protect the muscles from IR injury. FO given after IR injury can better downregulate the inflammation seen in IR‐induced remote kidney injury.