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.
†Nestlé Institute of Health Sciences SA, Molecular Biomarkers Dpt, EPFL Innovation Park, Building H, 1015 Lausanne, Switzerland.
Francois-Pierre J
FP
Martin
‡Technische Universität München, Chair of Nutrition and Immunology, ZIEL-Research Center for Nutrition and Food Sciences, Gregor-Mendel-Strasse 2, 85350 Freising-Weihenstephan, Germany.
Pia
P
Lichti
§Nestlé Research Center, Nutrition and Health Department, 1000 Lausanne, Switzerland.
Nabil
N
Bosco
§Nestlé Research Center, Nutrition and Health Department, 1000 Lausanne, Switzerland.
Viral
V
Brahmbhatt
§Nestlé Research Center, Nutrition and Health Department, 1000 Lausanne, Switzerland.
Manuel
M
Oliveira
‡Technische Universität München, Chair of Nutrition and Immunology, ZIEL-Research Center for Nutrition and Food Sciences, Gregor-Mendel-Strasse 2, 85350 Freising-Weihenstephan, Germany.
Dirk
D
Haller
§Nestlé Research Center, Nutrition and Health Department, 1000 Lausanne, Switzerland.
Jalil
J
Benyacoub
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D003092:Colitis / Q000378:metabolism* / Q000517:prevention & control*; D019587:Dietary Supplements; D005243:Feces / Q000737:chemistry; D005395:Fish Oils / Q000494:pharmacology*; D005973:Glutamine / Q000032:analysis; D007656:Ketoglutaric Acids / Q000032:analysis; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome / Q000187:drug effects / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D019802:Succinic Acid / Q000032:analysis; D014556:Urine / Q000737:chemistry
D005395:Fish Oils; D007656:Ketoglutaric Acids; D005973:Glutamine; D019802:Succinic Acid
Chemometrics; Fish oil; Inflammatory bowel disease (IBD); Liver; Metabonomics; Nuclear magnetic resonance (NMR) spectroscopy; Omega-3 fatty acids; Plasma; Stool; Urine