title: Over-expression of TLR4-CD14, pro-inflammatory cytokines, metabolic markers and NEFAs in obese non-diabetic Mexicans.
abstract: BACKGROUND
  Obesity 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.
  
  
  METHODS
  A 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-1β = 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-α =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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Doctorado en Ciencias Biomédicas, Guadalajara, Jal, México.
authors.forename: Cesar Octavio
authors.initials: CO
authors.lastname: De Loera-Rodriguez
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jal, México.
authors.forename: Vidal
authors.initials: V
authors.lastname: Delgado-Rizo
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jal, México.
authors.forename: Anabell
authors.initials: A
authors.lastname: Alvarado-Navarro
authors.affiliation: Doctorado en Ciencias Biomédicas, Guadalajara, Jal, México.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Agraz-Cibrian
authors.affiliation: Servicio de Gastroenterología, Antiguo Hospital Civil de Guadalajara ¨Fray Antonio Alcalde¨, Guadalajara, Jal, México.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Segura-Ortega
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jal, México.
authors.forename: Mary
authors.initials: M
authors.lastname: Fafutis-Morris
keywords: Inflammatory cytokines; Metabolic markers; NEFAs; Obesity; TLR4