Blueberry treatment improves renal function and reduces oxidative stress in Metabolic Syndrome animals – Role of Toll‐like receptor 4 (TLR4)

Background: Our previous study revealed that astragaloside IV (AS-IV) effectively improved gestational diabetes mellitus (GDM) by reducing hepatic gluconeogenesis. Due to the importance of placental oxidative stress, we further explored the protective role of AS-IV on placental oxidative stress in GDM. Methods: First, non-pregnant mice were orally administrated with AS-IV to evaluate its safety and effect. Then GDM mice were orally administered with AS-IV for 20 days and its effect on the symptoms of GDM, placental oxidative stress, secretions of inflammatory cytokines, as well as toll-like receptor 4 (TLR4)/NF-κB signaling pathway, were evaluated. Results: AS-IV had no adverse effect on non-pregnant mice. On the other hand, AS-IV significantly attenuated the GDM-induced hyperglycemia, glucose intolerance, insulin resistance, placental oxidative stress, productions of inflammatory cytokines and the activation of TLR4/NF-κB pathway. Conclusion: AS-IV effectively protected against GDM by alleviating placental oxidative stress and inflammation, in which TLR4/NF-κB might be involved.

Download Full-text

Faculty Opinions recommendation of Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edema.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1283990.751098 ◽

2009 ◽

Author(s):

Matthias Ochs ◽

Christian Mühlfeld

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Critical Role ◽

Toll Like Receptor ◽

Toll Like Receptor 4

Download Full-text

Abrogation of Toll-Like Receptor 4 Mitigates Obesity-Induced Oxidative Stress, Proinflammation, and Insulin Resistance Through Metabolic Reprogramming of Mitochondria in Adipose Tissue

Antioxidants and Redox Signaling ◽

10.1089/ars.2019.7737 ◽

2020 ◽

Vol 33 (2) ◽

pp. 66-86 ◽

Cited By ~ 2

Author(s):

Hung-Yu Lin ◽

Shao-Wen Weng ◽

Feng-Chih Shen ◽

Yen-Hsiang Chang ◽

Wei-Shiung Lian ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Adipose Tissue ◽

Metabolic Reprogramming ◽

Toll Like Receptor ◽

Toll Like Receptor 4

Download Full-text

Understanding the role of oxidative stress in the incidence of metabolic syndrome and obstructive sleep apnea

BMC Endocrine Disorders ◽

10.1186/s12902-021-00735-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Behnam Kargar ◽

Zahra Zamanian ◽

Majid Bagheri Hosseinabadi ◽

Vahid Gharibi ◽

Mohammad Sanyar Moradi ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Obstructive Sleep Apnea ◽

Logistic Regression ◽

Sleep Apnea ◽

International Diabetes Federation ◽

Binary Logistic Regression ◽

Stress Index ◽

Obstructive Sleep

Abstract Background Understanding the causes and risk factors of metabolic syndrome is important for promoting population health. Oxidative stress has been associated with metabolic syndrome, and also obstructive sleep apnea. These are two diseases which have common prognostic characteristics for heart disease. The aim of this study was to examine the role of oxidative stress in the concurrent presence of metabolic syndrome and obstructive sleep apnea in a working population. Methods Participants were 163 artisan bakers in Shahroud, Iran, routinely exposed to significant heat stress and other oxidative stress indicators on a daily basis as part of their work. Using a cross-sectional design, data relevant to determining metabolic syndrome status according to International Diabetes Federation criteria, and the presence of obstructive sleep apnea according to the STOP-Bang score, was collected. Analyses included hierarchical binary logistic regression to yield predictors of the two diseases. Results Hierarchical binary logistic regression showed that oxidative stress – alongside obesity, no regular exercise, and smoking – was an independent predictor of metabolic syndrome, but not obstructive sleep apnea. Participants who were obese were 28 times more likely to have metabolic syndrome (OR 28.59, 95% CI 4.91–63.02) and 44 times more likely to have obstructive sleep apnea (OR 44.48, 95% CI 4.91–403.28). Participants meeting metabolic syndrome criteria had significantly higher levels of malondialdehyde (p < 0.05) than those who did not. No difference in oxidative stress index levels were found according to obstructive sleep apnea status. Conclusions Our findings suggest that oxidative stress contributes to the onset of metabolic syndrome, and that obstructive sleep apnea is involved in oxidative stress. Whilst obesity, exercise, and smoking remain important targets for reducing the incidence of metabolic syndrome and obstructive sleep apnea, policies to control risks of prolonged exposure to oxidative stress are also relevant in occupations where such environmental conditions exist.

Download Full-text

Cateslytin abrogates lipopolysaccharide-induced cardiomyocyte injury by reducing inflammation and oxidative stress through toll like receptor 4 interaction

International Immunopharmacology ◽

10.1016/j.intimp.2021.107487 ◽

2021 ◽

Vol 94 ◽

pp. 107487

Author(s):

Carmine Rocca ◽

Anna De Bartolo ◽

Fedora Grande ◽

Bruno Rizzuti ◽

Teresa Pasqua ◽

...

Keyword(s):

Oxidative Stress ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

And Oxidative Stress

Download Full-text

Role of genetic variants of Vitamin D receptor, Toll-like receptor 2 and Toll-like receptor 4 in extrapulmonary tuberculosis

Microbial Pathogenesis ◽

10.1016/j.micpath.2021.104911 ◽

2021 ◽

pp. 104911

Author(s):

Bilal Ahmad Wani ◽

Faheem Shehjar ◽

Sonaullah Shah ◽

Ajaz Koul ◽

Adfar Yusuf ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Genetic Variants ◽

Extrapulmonary Tuberculosis ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Toll Like Receptor 2

Download Full-text

Detrimental Role of Heat Shock Protein 60&70 and Toll-like Receptor 4 in Skeletal Muscle Ischaemia In Vitro

Journal of Vascular Surgery ◽

10.1016/j.jvs.2013.02.134 ◽

2013 ◽

Vol 57 (5) ◽

pp. 77S

Author(s):

Ali Navi ◽

Rebekah Yu ◽

Xu Shi-Wen ◽

Sidney Shaw ◽

George Hamilton ◽

...

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 60 ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Muscle Ischaemia

Download Full-text

Contrasting effects of the Toll-like receptor 4 in determining ovarian follicle endowment and fertility in female adult mice

Zygote ◽

10.1017/s096719942100054x ◽

2021 ◽

pp. 1-7

Author(s):

Júlio Panzera Gonçalves ◽

Breno Augusto Magalhães ◽

Paulo Henrique Almeida Campos-Junior

Keyword(s):

Ovarian Follicle ◽

Cumulus Cells ◽

Toll Like Receptor ◽

Female Reproduction ◽

Toll Like Receptor 4 ◽

Genetic Ablation ◽

Adult Mice ◽

Cumulus Oocyte Complex ◽

Estrous Cyclicity

Abstract Toll-like receptor 4 (TLR4) is best known for its role in bacteria-produced lipopolysaccharide recognition. Regarding female reproduction, TLR4 is expressed by murine cumulus cells and participates in ovulation and in cumulus–oocyte complex (COC) expansion, maternal–fetal interaction and preterm labour. Despite these facts, the role of TLR4 in ovarian physiology is not fully understood. Therefore, the aim of the present study was to investigate the effects of TLR4 genetic ablation on mice folliculogenesis and female fertility, through analysis of reproductive crosses, ovarian responsiveness and follicular quantification in TLR4−/− (n = 94) and C57BL/6 mice [wild type (WT), n = 102]. TLR4-deficient pairs showed a reduced number of pups per litter (P = 0.037) compared with WT. TLR4−/− mice presented more primordial, primary, secondary and antral follicles (P < 0.001), however there was no difference in estrous cyclicity (P > 0.05). A lower (P = 0.006) number of COC was recovered from TLR4−/− mice oviducts after superovulation, and in heterozygous pairs, TLR4−/− females also showed a reduction in the pregnancy rate and in the number of fetuses per uterus (P = 0.007) when compared with WT. Altogether, these data suggest that TLR4 plays a role in the regulation of murine folliculogenesis and in determining ovarian endowment. TLR4 deficiency may affect ovulation and pregnancy rates, potentially decreasing fertility, therefore the potential side effects of its blockade have to be carefully investigated.

Download Full-text

Abstract 1766: Diet-Induced Obesity Causes Inflammation by Activating Toll-Like Receptor 4 Signaling and Downregulates AMPK in Heart

Circulation ◽

10.1161/circ.118.suppl_18.s_385-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Hwi Jin Ko ◽

Dae Young Jung ◽

Zhexi Ma ◽

Jason K Kim

Keyword(s):

Glucose Metabolism ◽

Whole Body ◽

Chow Diet ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Myocardial Glucose Metabolism ◽

Cardiac Inflammation ◽

Protein Levels ◽

Diet Induced Obesity

Increasing evidence implicates the role of inflammation in diabetes and complications. Macrophages are shown to infiltrate adipose tissue in obesity, and inflammatory cytokines alter glucose metabolism in peripheral organs. Male C57BL/6 mice were fed high-fat diet (HFD; 55% fat by calories) or chow diet for 6 weeks, and heart samples were taken for analysis (n = 5~7). Chronic HFD increased whole body fat mass, measured by 1 H-MRS, by 3-fold, and elevated plasma IL-6 and TNF-α levels by 40%. Diet-induced obesity caused inflammation in heart and increased macrophage-specific CD68 levels by 5-fold (Fig. 1) (* P < 0.05 vs Chow). Diet-induced cardiac inflammation was associated with significant increases in toll-like receptor 4 (TLR4) and MyD88 levels in heart (Fig. 2). HFD also increased cardiomyocyte SOCS3 levels by more than 3-fold (Fig. 3). Myocardial glucose metabolism was measured using intravenous injection of 2-[ 14 C]deoxyglucose in awake mice (n = 6). Chronic HFD reduced myocardial glucose uptake by 50%, and this was associated with significant reductions in total GLUT4 and GLUT1 protein levels. Further, Thr 172 phosphorylation of AMPK, a critical regulator of energy balance, was markedly reduced in heart following HFD (Fig. 4). These results demonstrate that diet-induced obesity causes macrophage infiltration and inflammation in heart by increasing TLR4 signaling in cardiomyocytes. Similar to the effects of inflammation on peripheral glucose metabolism, diet-induced cardiac inflammation reduced myocardial glucose metabolism by downregulating AMPK and GLUT protein levels. Thus, our findings underscore an important role of inflammation in diabetic heart.

Download Full-text