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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

Serum cytokine concentration. The serum cytokine from lean and obese groups were measured by ELISA. Cytokines expressions are shown in pg/mL for each group. Results expressed the cytokines levels on serum and are represented as means ± SD values. A strong association of IL-6 and TNF-α with obesity was observed (*p < 0.05).
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Fig2: Serum cytokine concentration. The serum cytokine from lean and obese groups were measured by ELISA. Cytokines expressions are shown in pg/mL for each group. Results expressed the cytokines levels on serum and are represented as means ± SD values. A strong association of IL-6 and TNF-α with obesity was observed (*p < 0.05).

Mentions: The concentration of IL-6 and TNFα (36 pg/ml vs 31 pg/ml) in serum was greater in the obese and was statistically more significant in comparison to the individuals of normal weight (28 pg/ml vs 15 pg/ml), respectively (p <0,05). The concentration of IL-1 β in serum, IL-8, and IL-10 were not statistically significant when comparing obese and non- obese individuals (Figure 2).Figure 2


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)

Serum cytokine concentration. The serum cytokine from lean and obese groups were measured by ELISA. Cytokines expressions are shown in pg/mL for each group. Results expressed the cytokines levels on serum and are represented as means ± SD values. A strong association of IL-6 and TNF-α with obesity was observed (*p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Serum cytokine concentration. The serum cytokine from lean and obese groups were measured by ELISA. Cytokines expressions are shown in pg/mL for each group. Results expressed the cytokines levels on serum and are represented as means ± SD values. A strong association of IL-6 and TNF-α with obesity was observed (*p < 0.05).
Mentions: The concentration of IL-6 and TNFα (36 pg/ml vs 31 pg/ml) in serum was greater in the obese and was statistically more significant in comparison to the individuals of normal weight (28 pg/ml vs 15 pg/ml), respectively (p <0,05). The concentration of IL-1 β in serum, IL-8, and IL-10 were not statistically significant when comparing obese and non- obese individuals (Figure 2).Figure 2

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