title: Protective effects of fish oil on pre-diabetes: a lipidomic analysis of liver ceramides in rats.
abstract: A high intake of fat and sucrose can dramatically increase bioactive lipids such as ceramides in tissues. Ceramides regulate several steps in the insulin signal pathway. The effects of n-3 PUFA on insulin resistance are inconsistent, especially in liver. We investigated the effect of n-3 PUFA (EPA/DHA 1 : 1) from fish oil on hepatic ceramides in a pre-diabetic animal model. Three groups of rats were fed standard feed, high fat high sucrose feed (HFHS) or HFHS enriched with n-3 PUFA. We investigated by lipidomic analysis how supplementation of a HFHS diet with n-3 PUFA modifies the hepatic ceramide profile triggered by a HFHS diet. Our results show that n-3 PUFA modified the ceramide profile of the liver and reduced their total content in pre-diabetic rats. Significant linear correlations were observed between ceramides and biochemical insulin parameters. Long chain ceramide 18:1/18:0 showed a positive correlation with the HOMA index. Very long chain ceramide 18:1/24:0 showed a negative correlation with insulin and the HOMA index. Finally, very long chain ceramide 18:1/20:0 correlated negatively with glucose levels, plasmatic insulin levels and the HOMA index. In conclusion, the modulation of the ceramide profile in pre-diabetic rats may explain the protective action of n-3 PUFA against liver insulin resistance (IR) caused by an HFHS diet. We confirm the protective role of very long chain ceramide 18:1/24:0 and the harmful role of long chain ceramide 18:1/18:0 in the pre-diabetic state and propose ceramide 18:1/20:0 as a biomarker of early liver IR in rats.
authors.affiliation: Pharmacology Unit, Faculty of Medicine and Health Science, Rovira i Virgili University, Reus, Spain. marta.romeu@urv.cat.
authors.forename: Núria
authors.initials: N
authors.lastname: Taltavull
authors.affiliation: Center for Omics Sciences, Rovira i Virgili University, Reus, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Ras
authors.affiliation: Center for Omics Sciences, Rovira i Virgili University, Reus, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Mariné
authors.affiliation: Pharmacology Unit, Faculty of Medicine and Health Science, Rovira i Virgili University, Reus, Spain. marta.romeu@urv.cat.
authors.forename: Marta
authors.initials: M
authors.lastname: Romeu
authors.affiliation: Pharmacology Unit, Faculty of Medicine and Health Science, Rovira i Virgili University, Reus, Spain. marta.romeu@urv.cat.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Giralt
authors.affiliation: Institute of Marine Research (IIM-CSIC), Vigo, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Méndez
authors.affiliation: Institute of Marine Research (IIM-CSIC), Vigo, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Medina
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ramos-Romero
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.
authors.forename: Josep L
authors.identifier: http://orcid.org/0000-0002-5072-8265
authors.initials: JL
authors.lastname: Torres
authors.affiliation: Pharmacology Unit, Faculty of Medicine and Health Science, Rovira i Virgili University, Reus, Spain. marta.romeu@urv.cat.
authors.forename: M Rosa
authors.initials: MR
authors.lastname: Nogués
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002518:Ceramides / Q000737:chemistry / Q000378:metabolism*; D066273:Diet, Western / Q000009:adverse effects; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D008053:Lipid Mobilization; D008099:Liver / Q000378:metabolism*; D055432:Metabolomics / Q000379:methods; D008970:Molecular Weight; D011236:Prediabetic State / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D011921:Rats, Inbred WKY
chemical_list: D015415:Biomarkers; D002518:Ceramides; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents