Over-expression of TLR4-CD14, pro-inflammatory cytokines, metabolic markers and NEFAs in obese non-diabetic Mexicans (Journal of Inflammation)

IntroductionObesity is the world?s most important public health problem. Adipose tissue contributes significantly to increase pro-inflammatory mediators whose cascade begins with the union of TLR4 to its microbial ligands (TLR: Toll Like Receptors). It has been reported recently that NEFAs (Non-Esterified Fatty Acids) bind to this receptor as agonists. The purpose of our study was to determine the levels of expression of TLR4-CD14, the pro-inflammatory cytokines, the metabolic markers and the NEFAs in a group of adult, non-diabetic obese Mexicans.MethodA group of 210 adult middle-class Mexican non-diabetic obese patients was evaluated: 105 normal weight individuals, and 105 non-diabetic obese. On both groups, the following was tested in each patient: TLR4-CD14 receptors on monocytes in peripheral blood, inflammatory profile, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), NEFAs and each individual?s anthropometric profile. Results: Obesity is strongly associated with the expression of TLR4 (77%, MFI (Mean Fluorescence Index) 7.70) and CD14 (86% MFI 1.61) with 66% double positives (p?=?0.000). These figures contrast with those for the normal weight individuals that constituted the control group: TLR4 (70% MFI 6.41) and CD14 (84% MFI 1.25) with 59% double positives. As for cytokine concentration, non- diabetic obese individuals vs the normal weight/thin, the numbers were: IL-1?=?2.0 vs 2.5?pg/ml (p?=?NS), IL-6?=?36 vs 28?pg/ml (p =0.030), IL-8?=?27 vs 27?pg/ml (p?=?NS), IL-10?=?8.4 vs 6.8?pg/ml (p?=?NS), TNF-? =31 vs 15?pg/ml (p =0.000) respectively. Insulin levels were 12.1 vs 19.7 mcU/ml (p =0.000) and the NEFAs were much higher in the obese vs normal weight/thin individuals (p =0.000). Conclusion: Adipose tissue used to be thought of as mere storage of fats and energy, but it has been revealed to be an important neuro-immune-endocrine organ. Immune cells, stimulated by NEFAs, produce pro-inflammatory cytokines, which have a direct effect on oxidating radicals that directly target the release of noradrenalin. This in turn, reactivates the vicious cycle of low-grade chronic inflammation, as is now described in obesity.