Acute and chronic saturated fatty acid treatment as a key instigator of the TLR-mediated inflammatory response in human adipose tissue, in vitro

• Published in: The Journal of Nutritional Biochemistry Vol. 23; no. 1; pp. 39 - 50
• Main Authors: Youssef-Elabd, Elham M, McGee, Kirsty C, Tripathi, Gyanendra, Aldaghri, Nasser, Abdalla, Mohga S, Sharada, Hayat M, Ashour, Esmat, Amin, Ashraf I, Ceriello, Antonio, O'Hare, Joseph P, Kumar, Sudhesh, McTernan, Philip G, Harte, Alison L
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2012; Elsevier BV; Elsevier; Elsevier Science
• Subjects: acid treatment; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipose Tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adult; adverse effects; Biochemistry; Biological and medical sciences; chemically induced; Clinical Biochemistry; drug effects; Endocrinology, Diabetes and Metabolism; explants; Fatty Acids; Fatty Acids - adverse effects; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose; Glucose - pharmacology; Human adipose tissue; Humans; I-kappa B Kinase; I-kappa B Kinase - metabolism; In Vitro Techniques; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Interleukin-6; Interleukin-6 - secretion; memory; metabolism; Middle Aged; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 8 - metabolism; Mitogen-Activated Protein Kinase 9; Mitogen-Activated Protein Kinase 9 - metabolism; Molecular Biology; Myeloid Differentiation Factor 88; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B; NF-kappa B - metabolism; noninsulin-dependent diabetes mellitus; Nutrition and Dietetics; Obesity; patients; pharmacology; Saturated fatty acids; secretion; Signal Transduction; TNF Receptor-Associated Factor 6; TNF Receptor-Associated Factor 6 - metabolism; Toll-Like Receptor 4; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Toxicity Tests, Chronic; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - secretion; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Toll-like receptors; Obesity; Inflammation; Glucose; Saturated fatty acids; Human adipose tissue; Human; Adipose tissue; Acute; Nutrition disorder; Lipids; Toll like receptor; In vitro; Vertebrata; Chronic; Mammalia; Treatment; Saturated fatty acid; Nutritional status
• ISSN: 0955-2863; 1873-4847; 1873-4847
• DOI: 10.1016/j.jnutbio.2010.11.003

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.