Effects of increase in fish oil intake on intestinal eicosanoids and inflammation in a mouse model of colitis

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory diseases affecting about 1% of western populations. New eating behaviors might contribute to the global emergence of IBD. Although the immunoregulatory effects of omega-3 fatty acids have been well characterized in vitro, their role in IBD is controversial. METHODS: The aim of this study was to assess the impact of increased fish oil intake on colonic gene expression, eicosanoid metabolism and development of colitis in a mouse model of IBD. Rag-2 deficient mice were fed fish oil (FO) enriched in omega-3 fatty acids i.e. EPA and DHA or control diet for 4 weeks before colitis induction by adoptive transfer of naïve T cells and maintained in the same diet for 4 additional weeks. Onset of colitis was monitored by colonoscopy and further confirmed by immunological examinations. Whole genome expression profiling was made and eicosanoids were measured by HPLC-MS/MS in colonic samples. RESULTS: A significant reduction of colonic proinflammatory eicosanoids in FO fed mice compared to control was observed. However, neither alteration of colonic gene expression signature nor reduction in IBD scores was observed under FO diet. CONCLUSION: Thus, increased intake of dietary FO did not prevent experimental colitis

Comparative study of serine-plasmalogens in human retina and optic nerve: identification of atypical species with odd carbon chains

International audienceThe objective of this work was to detect and identify phosphatidylserine plasmalogen species in human ocular neurons represented by the retina and the optic nerve. Plasmalogens (vinyl-ether bearing phospholipids) are commonly found in the forms of phosphatidylcholine and phosphatidylethanolamine in numerous mammalian cell types, including the retina. While their biological functions are still unclear, the alteration of cellular plasmalogen content has been associated with several human disorders such as Rhizomelic Chondrodysplasia Punctata Type 2 and Primary Open-Angle Glaucoma.By using liquid-chromatography coupled to high resolution and tandem mass spectrometry, we have identified for the first time several species of phosphatidylserine plasmalogens including atypical forms having moieties with odd numbers of carbons and unsaturation in sn-2 position. Structural elucidation of the potential phosphatidylserine ether linked species was pursued by performing MS3 experiments and three fragments are proposed as marker ions to deduce which fatty acid is linked as ether or ester on the glycerol backbone. Interpretation of the fragmentation patterns based on this scheme enabled the assignment of structures to the m/z values this way identifying the phosphatidylserine plasmalogens

Early biomarkers of age-related low-grade inflammation

The present invention relates to a method for predicting the risk of acquiring an age-related low-grade inflammation for a subject, said method comprising a) providing a biological sample from a subject, b) determining in said sample the level of at least one biomarker selected from the group consisting of a compound of molecular weight between 859-863 g/mol and which is an alkylacylphosphatidylcholine, a compound of molecular weight between 861-86 g/mol and which is a diacylphosphatidylcholine, a compound of molecular weight between 791-794 g/mol and which is an alkylacylphosphatidylcholine, a compound of molecular weight between 522-525 g/mol and which is a monoacylphosphatidylcholine, octadecanoylcarnitine (C18), and tryptophan, c) comparing the level of the at least one biomarker to a reference level, and d) determining whether said subject is likely to be at risk of acquiring an age-related low-grade inflammation, when the level of biomarker(s) deviate significantly from the respective reference level

Early biomarkers of age-related low-grade inflammation

The present invention relates to a method for predicting the risk of acquiring an age-related low-grade inflammation for a subject, said method comprising a) providing a biological sample from a subject, b) determining in said sample the level of at least one biomarker selected from the group consisting of a compound of molecular weight between 859-863 g/mol and which is an alkylacylphosphatidylcholine, a compound of molecular weight between 861-86 g/mol and which is a diacylphosphatidylcholine, a compound of molecular weight between 791-794 g/mol and which is an alkylacylphosphatidylcholine, a compound of molecular weight between 522-525 g/mol and which is a monoacylphosphatidylcholine, octadecanoylcarnitine (C18), and tryptophan, c) comparing the level of the at least one biomarker to a reference level, and d) determining whether said subject is likely to be at risk of acquiring an age-related low-grade inflammation, when the level of biomarker(s) deviate significantly from the respective reference level

Metabolic Phenotyping of an Adoptive Transfer Mouse Model of Experimental Colitis and Impact of Dietary Fish Oil Intake

Inflammatory bowel diseases are acute and chronic disabling inflammatory disorders with multiple complex etiologies that are not well-defined. Chronic intestinal inflammation has been linked to an energy-deficient state of gut epithelium with alterations in oxidative metabolism. Plasma-, urine-, stool-, and liver-specific metabonomic analyses are reported in a naïve T cell adoptive transfer (AT) experimental model of colitis, which evaluated the impact of long-chain n-3 polyunsaturated fatty acid (PUFA)-enriched diet. Metabolic profiles of AT animals and their controls under chow diet or fish oil supplementation were compared to describe the (i) consequences of inflammatory processes and (ii) the differential impact of n-3 fatty acids. Inflammation was associated with higher glycoprotein levels (related to acute-phase response) and remodeling of PUFAs. Low triglyceride levels and enhanced PUFA levels in the liver suggest activation of lipolytic pathways that could lead to the observed increase of phospholipids in the liver (including plasmalogens and sphingomyelins). In parallel, the increase in stool excretion of most amino acids may indicate a protein-losing enteropathy. Fecal content of glutamine was lower in AT mice, a feature exacerbated under fish oil intervention that may reflect a functional relationship between intestinal inflammatory status and glutamine metabolism. The decrease in Krebs cycle intermediates in urine (succinate, α-ketoglutarate) also suggests a reduction in the glutaminolytic pathway at a systemic level. Our data indicate that inflammatory status is related to this overall loss of energy homeostasis

Metabolic Phenotyping of the Crohn's Disease-like IBD Etiopathology in the TNF^ΔARE/WT Mouse Model

The underlying biochemical consequences of inflammatory bowel disease (IBD) on the systemic and gastrointestinal metabolism have not yet been fully elucidated but could help to better understand the disease pathogenesis and to identify tissue-specific markers associated with the different disease stages. Here, we applied a metabonomic approach to monitor metabolic events associated with the gradual development of Crohn's disease (CD)-like ileitis in the TNF^ΔARE/WT mouse model. Metabolic profiles of different intestinal compartments from the age of 4 up to 24 weeks were generated by combining proton nuclear magnetic resonance (¹H NMR) spectroscopy and liquid chromatography–mass spectrometry (LC–MS). From 8 weeks onward, mice developed CD similar to the immune and tissue-related phenotype of human CD with ileal involvement, including ileal histological abnormalities, reduced fat mass and body weight, as well as hallmarks of malabsorption with higher energy wasting. The metabonomic approach highlighted shifts in the intestinal lipid metabolism concomitant to the histological onset of inflammation. Moreover, the advanced disease status was characterized by a significantly altered metabolism of cholesterol, triglycerides, phospholipids, plasmalogens, and sphingomyelins in the inflamed tissue (ileum) and the adjacent intestinal parts (proximal colon). These results describe different biological processes associated with the disease onset, including modifications of the general cell membrane composition, alteration of energy homeostasis, and finally the generation of inflammatory lipid mediators. Taken together, this provides novel insights into IBD-related alterations of specific lipid-dependant processes during inflammatory states

Designing programs to improve diets for maternal and child health: estimating costs and potential dietary impacts of nutrition-sensitive programs in Ethiopia, Nigeria, and India

Abstract Improving maternal and child nutrition in resource-poor settings requires effective use of limited resources, but priority-setting is constrained by limited information about program costs and impacts, especially for interventions designed to improve diet quality. This study utilized a mixed methods approach to identify, describe and estimate the potential costs and impacts on child dietary intake of 12 nutrition-sensitive programs in Ethiopia, Nigeria and India. These potential interventions included conditional livestock and cash transfers, media and education, complementary food processing and sales, household production and food pricing programs. Components and costs of each program were identified through a novel participatory process of expert regional consultation followed by validation and calibration from literature searches and comparison with actual budgets. Impacts on child diets were determined by estimating of the magnitude of economic mechanisms for dietary change, comprehensive reviews of evaluations and effectiveness for similar programs, and demographic data on each country. Across the 12 programs, total cost per child reached (net present value, purchasing power parity adjusted) ranged very widely: from 0.58 to 2650 USD/year among five programs in Ethiopia; 2.62 to 1919 USD/year among four programs in Nigeria; and 27 to 586 USD/year among three programs in India. When impacts were assessed, the largest dietary improvements were for iron and zinc intakes from a complementary food production program in Ethiopia (increases of 17.7 mg iron/child/day and 7.4 mg zinc/child/day), vitamin A intake from a household animal and horticulture production program in Nigeria (335 RAE/child/day), and animal protein intake from a complementary food processing program in Nigeria (20.0 g/child/day). These results add substantial value to the limited literature on the costs and dietary impacts of nutrition-sensitive interventions targeting children in resource-limited settings, informing policy discussions and serving as critical inputs to future cost-effectiveness analyses focusing on disease outcomes