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1.
JPEN J Parenter Enteral Nutr ; 42(2): 403-411, 2018 02.
Article in English | MEDLINE | ID: mdl-29187040

ABSTRACT

BACKGROUND: Replacement of parenteral soybean oil (SO) with fish oil (FO) is an effective therapy for intestinal failure-associated liver disease (IFALD) in children. However, practitioners remain concerned about the risk of essential fatty acid deficiency (EFAD) and sometimes treat IFALD with a combination of 50% SO and 50% FO emulsions. The purpose of this study was to determine if mixing 50% SO and 50% FO emulsions would prevent hepatosteatosis in a murine model of parenteral nutrition (PN)-induced hepatosteatosis. METHODS: C57BL/6 mice were randomized to receive oral PN with parenteral saline, FO, SO, or a mixture of 50% FO and 50% SO for 19 days. Fatty acid analysis, histologic evaluation, Nonalcoholic Steatohepatitis Clinical Research Network (NSCRN) scores, and reverse-transcriptase polymerase chain reaction for key lipogenic genes were performed. RESULTS: The PN + saline group was the only group with EFAD, with a serum and hepatic triene/tetraene ratio of 0.53. NSCRN scores were highest in the PN + SO group (5.5; 95% confidence interval [CI], 4.9-6.1), followed by the PN + FO/SO (4.5; 95% CI, 3.5-5.5) group, with the lowest score in the PN + FO (2.0; 95% CI, 1.1-2.9) group. Acetyl CoA carboxylase α and acetyl CoA carboxylase ß expression was lower in the PN + FO group than in the PN + FO/SO or PN + SO groups. CONCLUSIONS: Our data demonstrate that a mixed fat emulsion of 50% SO and 50% FO is inferior to 100% FO in reducing hepatosteatosis in this model. These data suggest that use of parenteral SO with parenteral FO, in a 1:1 ratio, may still contribute to liver injury, although it is less hepatotoxic than pure SO.


Subject(s)
Fish Oils/pharmacology , Liver Diseases/complications , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diet therapy , Parenteral Nutrition/methods , Soybean Oil/pharmacology , Animals , Disease Models, Animal , Fish Oils/administration & dosage , Male , Mice , Mice, Inbred C57BL , Soybean Oil/administration & dosage , Treatment Outcome
2.
Lipids ; 51(6): 703-14, 2016 06.
Article in English | MEDLINE | ID: mdl-27117864

ABSTRACT

Dietary strategies to alter the immune response to acute inflammation have the potential to improve outcomes in critically ill patients. A eucaloric ketogenic diet (EKD), composed predominantly of fat with very small amounts of carbohydrate, can provide adequate caloric support while minimizing spikes in blood glucose and reducing oxidative stress. The purpose of this study was to evaluate the effects of an EKD on glycemic control and the inflammatory response after acute endotoxemia in mice. Mice received either an EKD or a carbohydrate-based control diet (CD) for 4 weeks. Animals subsequently underwent either a 2-h fast (postprandial) or an overnight fast (postabsorptive), and half of the animals in each diet group were randomized to receive either intraperitoneal lipopolysaccharide (1 mg/kg) or an equivalent volume of saline. Glycemic response, insulin resistance, inflammatory cytokine levels, and the expression of key inflammatory and metabolic genes were measured. After endotoxin challenge, hypoglycemia was more frequent in mice fed a CD than an EKD in the postprandial period. This was due in part to the preservation of hepatic glycogen stores despite endotoxin exposure and prolonged fasting in mice fed an EKD. Furthermore, mice fed the CD had higher levels of IL-6 and TNF-α in the postabsorptive period, with a fivefold higher expression of hepatic NFκB compared to mice fed the EKD in both fasting periods. These results suggest that the unique metabolic state induced by an EKD can alter the response to acute inflammation in mice.


Subject(s)
Endotoxemia/complications , Hypoglycemia/diet therapy , Interleukin-6/genetics , Lipopolysaccharides/adverse effects , Tumor Necrosis Factor-alpha/genetics , Animals , Diet, Ketogenic , Endotoxemia/chemically induced , Endotoxemia/immunology , Gene Expression Regulation/drug effects , Insulin Resistance , Male , Mice , Postprandial Period , Treatment Outcome
3.
J Pediatr Surg ; 51(1): 56-61, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26548631

ABSTRACT

PURPOSE: We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis. METHODS: Rat fetuses (n=117) with surgically created gastroschisis were divided into three groups: untreated animals (n=62) and two groups receiving volume-matched intraamniotic injections of either saline (n=25) or 2 × 10(6) cells/mL of syngeneic, labeled afMSCs (n=30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P<0.05). RESULTS: Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P=0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P=0.003/0.05/<0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P=0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect. CONCLUSIONS: Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis.


Subject(s)
Fetal Therapies/methods , Gastroschisis/therapy , Intestines/pathology , Mesenchymal Stem Cell Transplantation/methods , Amnion , Amniotic Fluid/cytology , Animals , Female , Gastroschisis/pathology , Injections , Rats , Rats, Sprague-Dawley , Treatment Outcome
4.
J Surg Res ; 191(1): 148-55, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24793452

ABSTRACT

BACKGROUND: As low bone mineral density is a risk factor for fracture in childhood, optimizing age appropriate bone mass is recommended and might lower the impact of bone loss related to age. Consumption of omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic and docosahexaenoic (DHA) acids have been shown to beneficially modulate bone metabolism. The objective of this study was to determine the incidence of fracture in neonates receiving a fish compared with soybean oil-based intravenous lipid emulsion and evaluate the effect of varying dietary omega-3 PUFA consumption on growing bone in young mice. MATERIALS AND METHODS: Eligibility criteria for the clinical study included gestational age ≤37 wk and parenteral nutrition-dependence for ≥4 wk. Radiographs were reviewed after lipid initiation to identify radiologic bone fracture. The animal study evaluated female C57/Bl6 mice randomized into one of five groups from age 3-12 wk, at which time femurs were harvested for micro-computed tomography and light microscopy analysis. RESULTS: A lower incidence of bone fracture was found in neonates maintained on fish compared with soybean oil. In the animal study, findings suggest the DHA diet provides the best protection against trabecular bone loss as evidenced by increased bone volume fraction, increased trabecular number, and decreased trabecular separation on micro-computed tomography. These protective effects appeared to affect the bone microstructure alone. CONCLUSIONS: The lower fracture risk observed in fish oil fed neonates in combination with the protective effects of DHA observed in the femurs of young C57/BL6 mice suggest an important role for omega-3 PUFAs on bone growth.


Subject(s)
Bone Density/drug effects , Bone Development/drug effects , Docosahexaenoic Acids/pharmacology , Fractures, Bone/prevention & control , Animals , Eicosapentaenoic Acid/pharmacology , Fatty Acids, Omega-3/pharmacology , Female , Femur/diagnostic imaging , Femur/drug effects , Fish Oils/pharmacology , Fractures, Bone/diagnostic imaging , Fractures, Bone/etiology , Gastrointestinal Diseases/complications , Gestational Age , Humans , Infant, Newborn , Mice, Inbred C57BL , Osteoblasts/drug effects , Osteoblasts/pathology , Retrospective Studies , Soybean Oil/pharmacology , X-Ray Microtomography
5.
J Surg Res ; 188(2): 451-8, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24576779

ABSTRACT

BACKGROUND: To determine the effect of docosahexaenoic acid (DHA) on the growth of human melanoma in vitro and in vivo and to better understand the potential role of the G protein-coupled receptors (GPRs) in mediating this effect. MATERIALS AND METHODS: For in vitro studies, human melanoma and control fibroblast cells were treated with DHA and TAK-875 (selective GPR40 agonist) and a cell viability assay was performed to determine cell counts. A murine subcutaneous xenograft model of human melanoma was used to test the effect of dietary treatment with an omega-3 fatty acid (FA) rich diet compared with an omega-6 FA rich diet on the growth of human melanoma in vivo. A similar animal model was used to test the effect of oral TAK-875 on the growth of established melanoma tumors in vivo. RESULTS: DHA has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals on the omega-3 FA rich diet were 69% smaller in weight (P = 0.005) and 76% smaller in volume compared with tumors from animals on the omega-6 FA rich diet. TAK-875 has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals treated with TAK-875 were 46% smaller in weight (P = 0.07), 62% smaller in volume (P = 0.03), and grew 77% slower (P = 0.04) compared with the placebo group. CONCLUSIONS: DHA and TAK-875 have a profound and selective inhibitory effect on the growth of human melanoma both in vitro and in vivo.


Subject(s)
Benzofurans/therapeutic use , Docosahexaenoic Acids/therapeutic use , Melanoma, Experimental/diet therapy , Melanoma, Experimental/drug therapy , Receptors, G-Protein-Coupled/metabolism , Sulfones/therapeutic use , Animals , Benzofurans/pharmacology , Cell Line, Tumor , Docosahexaenoic Acids/pharmacology , Humans , Melanoma, Experimental/metabolism , Mice , Receptors, G-Protein-Coupled/agonists , Sulfones/pharmacology , Xenograft Model Antitumor Assays
6.
Metabolism ; 62(4): 499-508, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23151438

ABSTRACT

OBJECTIVE: Essential fatty acids (EFA) are necessary for growth, development, and biological function, and must be acquired through the diet. While linoleic acid (LA) and alpha-linolenic acid (ALA) have been considered the true EFAs, we previously demonstrated that docosahexaenoic acid (DHA) and arachidonic acid (AA) taken together as the sole source of dietary fatty acids can prevent biochemical essential fatty acid deficiency (EFAD). This study evaluates the effect of varying dietary ratios of DHA:AA in the prevention and reversal of biochemical EFAD in a murine model. METHODS: Using a murine model of EFAD, we provided mice with 2.1% of daily caloric intake in varying DHA:AA ratios (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) for 19 days in association with a liquid high-carbohydrate fat-free diet to evaluate the effect on fatty acid profiles. In a second experiment, we evaluated the provision of varying DHA:AA ratios (20:1, 200:1, 100:0) on the reversal of biochemical EFAD. RESULTS: Mice provided with DHA and AA had no evidence of biochemical EFAD, regardless of the ratio (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) administered. Biochemical EFAD was reversed with DHA:AA ratios of 20:1, 200:1, and 100:0 following 3 and 5 weeks of dietary provision, although the 20:1 ratio was most effective in the reversal and stabilization of the triene:tetraene ratio. CONCLUSION: Provision of DHA and AA, at 2.1% of daily caloric intake in varying ratios can prevent biochemical evidence of EFAD and hepatic steatosis over the short-term, with a ratio of 20:1 DHA:AA most effectively reversing EFAD.


Subject(s)
Arachidonic Acid/pharmacology , Docosahexaenoic Acids/pharmacology , Fatty Acids, Essential/deficiency , Animals , Diet , Diet, Fat-Restricted , Dietary Carbohydrates/pharmacology , Dietary Fats/pharmacology , Fatty Acids, Nonesterified/blood , Fatty Acids, Nonesterified/metabolism , Fatty Acids, Unsaturated/metabolism , Female , Growth/drug effects , Liver/enzymology , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C57BL
7.
Aging Cell ; 11(6): 1046-54, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22978268

ABSTRACT

Women approaching advanced maternal age have extremely poor outcomes with both natural and assisted fertility. Moreover, the incidence of chromosomal abnormalities and birth defects increases with age. As of yet, there is no effective and practical strategy for delaying ovarian aging or improving oocyte quality. We demonstrate that the lifelong consumption of a diet rich in omega-3 fatty acids prolongs murine reproductive function into advanced maternal age, while a diet rich in omega-6 fatty acids is associated with very poor reproductive success at advanced maternal age. Furthermore, even short-term dietary treatment with a diet rich in omega-3 fatty acids initiated at the time of the normal age-related rapid decline in murine reproductive function is associated with improved oocyte quality, while short-term dietary treatment with omega-6 fatty acids results in very poor oocyte quality. Thus, omega-3 fatty acids may provide an effective and practical avenue for delaying ovarian aging and improving oocyte quality at advanced maternal age.


Subject(s)
Aging/drug effects , Dietary Fats/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Genetic Fitness/drug effects , Oocytes/drug effects , Reproduction/drug effects , Administration, Oral , Aging/physiology , Animals , Breeding , Coconut Oil , Fatty Acids, Omega-6/administration & dosage , Fatty Acids, Omega-6/adverse effects , Female , Genetic Fitness/physiology , Humans , Litter Size/drug effects , Male , Mice , Mice, Inbred C57BL , Oocytes/cytology , Oocytes/physiology , Plant Oils/administration & dosage , Reproduction/physiology , Soybean Oil/administration & dosage
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