title: Acute and chronic saturated fatty acid treatment as a key instigator of the TLR-mediated inflammatory response in human adipose tissue, in vitro.
abstract: A post-prandial increase in saturated fatty acids (SFAs) and glucose (Glc) activates an inflammatory response, which may be prolonged following restoration of physiological SFAs and Glc levels--a finding referred to as 'metabolic memory'. This study examined chronic and oscillating SFAs and Glc on the inflammatory signalling pathway in human adipose tissue (AT) and adipocytes (Ads) and determined whether Ads are subject to "metabolic memory." Abdominal (Abd) subcutaneous (Sc) explants and Ads were treated with chronic low glucose (L-Glc): 5.6 mM and high glucose (H-Glc): 17.5 mM, with low (0.2 mM) and high (2 mM) SFA for 48 h. Abd Sc explants and Ads were also exposed to the aforementioned treatment regimen for 12-h periods, with alternating rest periods of 12 h in L-Glc. Chronic treatment with L-Glc and high SFAs, H-Glc and high SFAs up-regulated key factors of the nuclear factor-κB (NFκB) pathway in Abd Sc AT and Ads (TLR4, NFκB; P<.05), whilst down-regulating MyD88. Oscillating Glc and SFA concentrations increased TLR4, NFκB, IKKβ (P<.05) in explants and Ads and up-regulated MyD88 expression (P<.05). Both tumor necrosis factor α and interleukin 6 (P<.05) secretion were markedly increased in chronically treated Abd Sc explants and Ads whilst, with oscillating treatments, a sustained inflammatory effect was noted in absence of treatment. Therefore, SFAs may act as key instigators of the inflammatory response in human AT via NFκB activation, which suggests that short-term exposure of cells to uncontrolled levels of SFAs and Glc leads to a longer-term inflammatory insult within the Ad, which may have important implications for patients with obesity and Type 2 diabetes.
authors.affiliation: Biochemistry Department, National Research Centre, Dokki, Giza, Egypt 12622.
authors.forename: Elham M
authors.initials: EM
authors.lastname: Youssef-Elabd
authors.forename: Kirsty C
authors.initials: KC
authors.lastname: McGee
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Tripathi
authors.forename: Nasser
authors.initials: N
authors.lastname: Aldaghri
authors.forename: Mohga S
authors.initials: MS
authors.lastname: Abdalla
authors.forename: Hayat M
authors.initials: HM
authors.lastname: Sharada
authors.forename: Esmat
authors.initials: E
authors.lastname: Ashour
authors.forename: Ashraf I
authors.initials: AI
authors.lastname: Amin
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.forename: Joseph P
authors.initials: JP
authors.lastname: O'Hare
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Philip G
authors.initials: PG
authors.lastname: McTernan
authors.forename: Alison L
authors.initials: AL
authors.lastname: Harte
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D005227:Fatty Acids / Q000009:adverse effects*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008875:Middle Aged; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D036401:Toxicity Tests, Chronic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D015850:Interleukin-6; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495345:TLR4 protein, human; D048029:TNF Receptor-Associated Factor 6; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D048056:Mitogen-Activated Protein Kinase 9; D051550:I-kappa B Kinase; D048055:Mitogen-Activated Protein Kinase 8; D005947:Glucose