The Effects of Nutrients on Toll Like Receptor Activated Inflammatory Pathways in Human Adipose Tissue, [italic]In Vitro[/italic] | American Diabetes Association
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The Effects of Nutrients on Toll Like Receptor Activated Inflammatory Pathways in Human Adipose Tissue, [italic]In Vitro[/italic] Chronic hyperlipidaemia and h Chronic hyperlipidaemia and hyperglycaemia are established as key factors in the pathogenesis of obesity mediated diabetes. Post-prandial increase in saturated fatty acids (SFAs) and glucose (Glc) activate an inflammatory response, which may be prolonged following restoration of physiological SFAs and Glc levels - a finding referred to as [apos]metabolic memory[apos]. Therefore, we investigated (1) the effect of chronic and oscillating SFAs and Glc on the inflammatory signalling pathway in human adipose tissue (AT) and adipocytes (Ad) and (2) determined whether AT/Ad are subject to [apos]metabolic memory[apos]. Abdominal (Abd) subcutaneous (Sc) AT was collected from patients undergoing elective surgery (age 45[plusmn]3.3 yrs; BMI: 21.9[plusmn]2.4 kg/m[sup]2[/sup]; n=6). Explants and Ad were treated with chronic low glucose (L-Glc): 5.6mM and high glucose (H-Glc): 17.5mM, with low (0.2 mM) and high (2 mM) SFA for 48hrs. Explants and Ad were also exposed to the aforementioned treatment regimen for 12hr periods, with alternating rest periods of 12hrs in L-Glc. Chronic treatment with L-Glc and high SFAs, H-Glc and high SFAs up-regulated key factors of the NF[kappa]B pathway in AbdSc AT explants and Ad (TLR4, NFkB; p[lt]0.05) whilst down-regulating MyD88. Oscillating Glc and SFA concentrations increased TLR4, NF[kappa]B, IKK[beta] (p[lt]0.05) in explants and Ad, which upregulated MYD88 expression (p[lt]0.05). Downstream both TNF[alpha] and IL-6 (p[lt]0.05) secretion were markedly increased in chronically treated explants and Ad whilst, with oscillating treatments, a sustained inflammatory effect was noted in absence of treatment. Hyperlipidaemia up-regulated the innate immune response in AbdSc AT explants and Ad with chronic and oscillating exposure. AbdSc explants and Ad were subject to [apos]metabolic memory[apos], differentially activated by the MyD88 dependent pathway, in contrast to the chronically treated cells. This study implicates elevated SFAs as a key instigator of the inflammatory response in both AT and Ad, via NF[kappa]B, which suggests that short-term exposure of cells to uncontrolled levels of SFAs and Glc lead to a longer-term inflammatory insult within the Ad, which may have important implications for patients with obesity and T2DM. ALISON L. HARTE, ELHAM M. M. YOUSSEF-ELABD, KIRSTY C. MCGEE, GYANENDRA TRIPATHI, MOHGA S. ABDALLA, HAYAT M. SHARADA, ESMAT ASHOUR, ASHRAF I. AMIN, ANTONIO CERIELLO, JOSEPH P. O[apos]HARE, SUDHESH KUMAR, PHILIP G. MCTERNAN 1501-P Coventry, United Kingdom, Dokki, Giza, Egypt, Helwan, Egypt, Cairo, Egypt Adipocyte Biology
70th Scientific Sessions (2010)
Adipocyte Biology