title: Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes.
abstract: Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. m.m.heemskerk@lumc.nl.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. m.m.heemskerk@lumc.nl.
authors.forename: Mattijs M
authors.initials: MM
authors.lastname: Heemskerk
authors.affiliation: Center of Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. m.a.giera@lumc.nl.
authors.forename: Martin
authors.initials: M
authors.lastname: Giera
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. f.el_bouazzaoui@lumc.nl.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. f.el_bouazzaoui@lumc.nl.
authors.forename: Fatiha El
authors.initials: FE
authors.lastname: Bouazzaoui
authors.affiliation: Department of Medicine, division Endocrinology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. m.a.lips@lumc.nl.
authors.forename: Mirjam A
authors.initials: MA
authors.lastname: Lips
authors.affiliation: Department of Medicine, division Endocrinology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. h.pijl@lumc.nl.
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.|Department of Medicine, division Endocrinology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. V.J.A.van_Harmelen@lumc.nl.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden 2300 RC, The Netherlands. V.J.A.van_Harmelen@lumc.nl.
authors.forename: Vanessa
authors.initials: V
authors.lastname: van Harmelen
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins / Q000235:genetics; D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis* / Q000235:genetics; D016718:Arachidonic Acid / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D004150:Dipeptidases / Q000235:genetics; D004281:Docosahexaenoic Acids / Q000032:analysis*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000201:enzymology*; D018836:Inflammation Mediators / Q000032:analysis*; D050152:Intra-Abdominal Fat / Q000201:enzymology; D015289:Leukotrienes / Q000032:analysis; D008875:Middle Aged; D009426:Netherlands; D009767:Obesity, Morbid / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000601:surgery; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000201:enzymology*; D015854:Up-Regulation; D000097382:CD68 Molecule
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001094:Arachidonate 5-Lipoxygenase; D016718:Arachidonic Acid; D004150:Dipeptidases; D004281:Docosahexaenoic Acids; D018836:Inflammation Mediators; D015289:Leukotrienes; C548592:ALOX5AP protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C583212:ALOX5 protein, human; C031499:CNDP2 protein, human
keywords: arachidonic acid; gene expression; leukotrienes; lipidomics; omega-3 fatty acids