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Over-expression of TLR4-CD14, pro-inflammatory cytokines, metabolic markers and NEFAs in obese non-diabetic Mexicans.

De Loera-Rodriguez CO, Delgado-Rizo V, Alvarado-Navarro A, Agraz-Cibrian JM, Segura-Ortega JE, Fafutis-Morris M - J Inflamm (Lond) (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Doctorado en Ciencias Biomédicas, Guadalajara, Jal, México.

ABSTRACT

Introduction: 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.

Method: 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).

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.

No MeSH data available.


Related in: MedlinePlus

Percentage and IFM of expression TLR4 and CD14. The expression of TLR4/CD14 was more in obese then lean individuals. a) Percentage CD14 expression. b) CD 14 mean fluorescence index. c) Percentage TLR4 expression. d) TLR4 mean fluorescence index. e) Percentage of positive double expression CD14-TLR4. The graphs show the mean ± SD of the results.
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Fig1: Percentage and IFM of expression TLR4 and CD14. The expression of TLR4/CD14 was more in obese then lean individuals. a) Percentage CD14 expression. b) CD 14 mean fluorescence index. c) Percentage TLR4 expression. d) TLR4 mean fluorescence index. e) Percentage of positive double expression CD14-TLR4. The graphs show the mean ± SD of the results.

Mentions: Monocyte population was identified based on size and granular characteristics in an EPICS XL-MCL flow cytometer (Beckman Coulter, Krefeld, Germany). A total of 10,000 CD14 + monocytes was read for each sample. The percentage of TLR4 + CD14+ monocytes was calculated from the analysis of the two fluorochromes (See Figure 1). Data was analyzed using FlowJo software (Arbol Star Inc., Ashland, Oregon, USA). Mean Fluorescence intensity (MFI) was determined subtracting the intensity of the geometric mean fluorescence from the sample control isotope.Figure 1


Over-expression of TLR4-CD14, pro-inflammatory cytokines, metabolic markers and NEFAs in obese non-diabetic Mexicans.

De Loera-Rodriguez CO, Delgado-Rizo V, Alvarado-Navarro A, Agraz-Cibrian JM, Segura-Ortega JE, Fafutis-Morris M - J Inflamm (Lond) (2014)

Percentage and IFM of expression TLR4 and CD14. The expression of TLR4/CD14 was more in obese then lean individuals. a) Percentage CD14 expression. b) CD 14 mean fluorescence index. c) Percentage TLR4 expression. d) TLR4 mean fluorescence index. e) Percentage of positive double expression CD14-TLR4. The graphs show the mean ± SD of the results.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4260202&req=5

Fig1: Percentage and IFM of expression TLR4 and CD14. The expression of TLR4/CD14 was more in obese then lean individuals. a) Percentage CD14 expression. b) CD 14 mean fluorescence index. c) Percentage TLR4 expression. d) TLR4 mean fluorescence index. e) Percentage of positive double expression CD14-TLR4. The graphs show the mean ± SD of the results.
Mentions: Monocyte population was identified based on size and granular characteristics in an EPICS XL-MCL flow cytometer (Beckman Coulter, Krefeld, Germany). A total of 10,000 CD14 + monocytes was read for each sample. The percentage of TLR4 + CD14+ monocytes was calculated from the analysis of the two fluorochromes (See Figure 1). Data was analyzed using FlowJo software (Arbol Star Inc., Ashland, Oregon, USA). Mean Fluorescence intensity (MFI) was determined subtracting the intensity of the geometric mean fluorescence from the sample control isotope.Figure 1

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Doctorado en Ciencias Biomédicas, Guadalajara, Jal, México.

ABSTRACT

Introduction: 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.

Method: 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).

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.

No MeSH data available.


Related in: MedlinePlus