Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation

Ahmad, Rasheed; Al‐Mass, Anfal; Atizado, Valerie; Alhubail, Asma; Al-Ghimlas, Fahad; Alarouj, Monira; Bennakhi, Abdullah; Dermime, Said; Behbehani, Kazem

doi:10.1186/1476-9255-9-48

Cited by 143 publications

(129 citation statements)

References 35 publications

(31 reference statements)

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“…19 Similarly, Ahmad et al also found a significantly increased expression of TLR2, TLR4, and MYD88 in both peripheral blood mononuclear cells and subcutaneous adipose tissue of obese and overweight subjects compared to lean controls. 20 In agreement with these reports, we detected a significant correlation between the gene expression of TLR4 in subcutaneous fat with the subcutaneous and visceral expression of MYD88. In addition, we detected a significant correlation between the subcutaneous and visceral expression of MYD88 with the expression of PAI-1 in both adipose tissues.…”

Section: Figsupporting

confidence: 81%

Expression ofMYD88in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome?

Cuevas

Lazo

Zúñiga

et al. 2017

Metabolic Syndrome and Related Disorders

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Background: The mechanism leading to the development of metabolic complications in obese individuals is not fully understood. Thus, the objective of this study was to examine differences in insulin resistance, inflammation, cytokine and adipokine levels, and expression of selected genes across obese individuals with different number of metabolic syndrome (MetS) components. Methods: Forty obese individuals who underwent bariatric surgery, divided in three groups based on the number of components of MetS, in addition to abdominal obesity (0, 1, and 2-3 additional components), were studied. Levels of inflammatory proteins, insulin resistance, cytokines, adipokines, and gene expression in subcutaneous (SAT) and visceral adipose tissue (VAT) were compared. Results: There was a significantly higher expression of MYD88 in SAT among those with more components of MetS (P = 0.008). In SAT, but not in VAT, MYD88 expression was significantly correlated with toll-like receptor 4 expression (r = 0.7, P < 0.05). Expression of adipsin in SAT was also associated with the presence of more components of MetS, but with borderline statistical significance (P = 0.05). There were no significant differences in insulin resistance, inflammation, and cytokine and adipokine levels by the number of components of MetS. Conclusions: Our study suggests that MYD88 expression in SAT of obese subjects could be associated with the development of components of MetS.

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Section: Figsupporting

confidence: 81%

Expression ofMYD88in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome?

Cuevas

Lazo

Zúñiga

et al. 2017

Metabolic Syndrome and Related Disorders

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“…TLR2 and TLR4 expression and activation are increased in bone marrow-derived macrophages of non-obese diabetic (NOD) mice, correlating with increased NF-κB activation and increased pro-inflammatory cytokines [33] . A clinical study showed that TLR2/4 mediated inflammation in monocytes was significantly correlated to the HbA1c levels in diabetic patients [34] . Furthermore, TLR4 has been reported to link the inflammatory responses of diabetes and periodontitis.…”

Section: Wwwchinapharcom Zhen L Et Almentioning

confidence: 99%

Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling

et al. 2014

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Aim: To investigate the therapeutic effects of resveratrol (RSV) on periodontitis in diabetic mice and to explore the underlying mechanisms in vitro. Methods: Experimental periodontitis was induced in db/db mice by ligature application of porphyromonas gingivalis. The mice were treated with RSV (20 mg/kg, po) daily for 4 weeks. Alveolar bone loss, proinflammatory cytokines and TLR4 expression in the gingival tissue were measured. Cultured gingival epithelial cells (GECs) were used for in vitro studies. The transcriptional activity of TLR4 downstream signaling was analyzed using Western blotting. Results: RSV administration significantly decreased the blood glucose levels, and ameliorated alveolar bone loss in db/db mice with experimental periodontitis. RSV administration also suppressed the high levels of IL-1β, IL-6, IL-8, TNF-α, and TLR4 in gingival tissue of the mice. In the GECs incubated in high glucose medium, TLR4 expression was substantially upregulated, which was partly blocked in the presence of RSV. Lipopolysaccharides markedly increased the expression and secretion of IL-1β, IL-6, IL-8, and TNF-α in the GECs cultured in high glucose medium, which was also partly blocked in the presence of RSV. Furthermore, RSV significantly suppressed the phosphorylation of TLR4 downstream factors NF-κB p65, p38MAPK, and STAT3. Conclusion: RSV exerts protective effects against experimental periodontitis in db/db mice via negative regulation of TLR4 signaling.

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“…Certain TLRs are known to be involved in metabolic inflammation, especially, the TLR4 has emerged as a metabolic sensor of lipopolysaccharide (LPS) as well as saturated free fatty acids (sFFAs) that are abundantly found in obese/T2D individuals [10]. Modulations in the expression of TLR1, TLR2, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9 have been reported in obesity and T2D [11-14]. Importantly, metabolic disease associated changes in the adipose tissue expression of TLR10 have remained unclear.…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

Sindhu

Akhter

Kochumon

et al. 2018

Cell Physiol Biochem

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Background/Aims: Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. Methods: TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H₂O₂) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student’s t-test and P<0.05 was considered significant. Results: The adipose tissue TLR10 gene/protein expression was found to be significantly upregulated in obesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H₂O₂-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Conclusion: Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation.

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Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation

Cited by 143 publications

References 35 publications

Expression ofMYD88in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome?

Expression ofMYD88in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome?

Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling

Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

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