title: Omega-3 fatty acid supplementation influences the whole blood transcriptome in women with obesity, associated with pro-resolving lipid mediator production.
abstract: The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8g EPA+DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray. Women supplemented with n-3 PUFAs for 3months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-α, NRF2 and NF-κB target genes. N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-α target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes.
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland. Electronic address: apolus@cm-uj.krakow.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Polus
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zapala
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Razny
authors.affiliation: Department of Molecular Biology and Clinical Genetics Laboratory, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gielicz
authors.affiliation: Department of Metabolic Disorders, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Malczewska-Malec
authors.affiliation: Department of Molecular Biology and Clinical Genetics Laboratory, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Childs
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Aldona
authors.initials: A
authors.lastname: Dembinska-Kiec
mesh_terms: D000328:Adult; D000368:Aged; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D015525:Fatty Acids, Omega-3; D008055:Lipids
keywords: DHA and EPA supplementation; Human obesity; Inflammation; Microarray; Pro-resolving mediators