scholarly journals Effect of Advanced Glycation End-Products and Excessive Calorie Intake on Diet-Induced Chronic Low-Grade Inflammation Biomarkers in Murine Models

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3091
Author(s):  
Matheus Thomaz Nogueira Silva Lima ◽  
Michael Howsam ◽  
Pauline M. Anton ◽  
Carine Delayre-Orthez ◽  
Frédéric J. Tessier
Keyword(s):  
Advanced Glycation End Products ◽  
Calorie Intake ◽  
Future Research ◽  
Low Grade ◽  
Physiological Effects ◽  
Murine Models ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Low Grade Inflammation

Chronic Low-Grade Inflammation (CLGI) is a non-overt inflammatory state characterized by a continuous activation of inflammation mediators associated with metabolic diseases. It has been linked to the overconsumption of Advanced Glycation End-Products (AGEs), and/or macronutrients which lead to an increase in local and systemic pro-inflammatory biomarkers in humans and animal models. This review provides a summary of research into biomarkers of diet-induced CLGI in murine models, with a focus on AGEs and obesogenic diets, and presents the physiological effects described in the literature. Diet-induced CLGI is associated with metabolic endotoxemia, and/or gut microbiota remodeling in rodents. The mechanisms identified so far are centered on pro-inflammatory axes such as the interaction between AGEs and their main receptor AGEs (RAGE) or increased levels of lipopolysaccharide. The use of murine models has helped to elucidate the local and systemic expression of CLGI mediators. These models have enabled significant advances in identification of diet-induced CLGI biomarkers and resultant physiological effects. Some limitations on the translational (murine → humans) use of biomarkers may arise, but murine models have greatly facilitated the testing of specific dietary components. However, there remains a lack of information at the whole-organism level of organization, as well as a lack of consensus on the best biomarker for use in CLGI studies and recommendations as to future research conclude this review.

scholarly journals Hepatic Fat Content and Liver Enzymes Are Associated with Circulating Free and Protein-Bound Advanced Glycation End Products, Which Are Associated with Low-Grade Inflammation: The CODAM Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Mitchell Bijnen ◽  
Marleen M. J. van Greevenbroek ◽  
Carla J. H. van der Kallen ◽  
Jean L. Scheijen ◽  
Marjo P. H. van de Waarenburg ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Liver Enzymes ◽  
Liver Fat ◽  
Low Grade ◽  
Advanced Glycation ◽  
Hepatocellular Damage ◽  
Glycation End Products ◽  
End Products ◽  
Fatty Livers ◽  
Low Grade Inflammation

Advanced glycation end products (AGEs) accumulate in fatty livers and may contribute to low-grade inflammation (LGI), potentially via their receptor, RAGE. It is unknown if the AGE accumulation in fatty livers results in elevated circulating AGEs. In a cohort study, we investigated the association of liver fat and hepatocellular damage with circulating AGEs and soluble RAGE (sRAGE) and subsequently the association of circulating AGEs and sRAGE with LGI. Cross-sectional associations of liver fat percentage (eLF%; ln-transformed) and liver enzymes (LE score; standardized) with circulating AGEs (free CML, CEL, and MG-H1 in nM and protein-bound CML, CEL, and pentosidine in nmol/mmol lysine; ln-transformed) and sRAGE (pg/ml, ln-transformed) and additionally of AGEs and sRAGE with LGI (standardized) were determined by multiple linear regression. eLF% was positively associated with circulating free CEL (β=0.090; 95% CI 0.041; 0.139) but inversely with protein-bound CML (β=−0.071; 95% CI -0.108; -0.034). Similarly, the LE score was positively associated with free CML (β=0.044; 95% CI 0.012; 0.076) and CEL (β=0.040; 95% CI 0.009; 0.072) but inversely with protein-bound CML (β=−0.037; 95% CI -0.060; -0.013). Free CML (β=0.297; 95% CI 0.049; 0.545) was positively associated with LGI, while protein-bound CML (β=−0.547; 95% CI -0.888; -0.207) was inversely associated, although this association was absent after adjustment for BMI. eLF% and LE score were not associated with sRAGE and sRAGE not with LGI after adjustment for BMI. Liver fat and enzymes were positively associated with circulating free AGEs, which were associated with LGI. In contrast, inverse relations were observed of liver fat and enzymes with circulating protein-bound AGEs and of protein-bound AGEs with LGI. These data suggest that hepatic steatosis and inflammation affect the formation and degradation of hepatic protein-bound AGEs resulting in elevated circulating free AGE levels. These alterations in AGE levels might influence LGI, but this is likely independent of RAGE.

scholarly journals Advanced Glycation End Products: Formation, Role in Diabetic Complications, and Potential in Clinical Applications

2020 ◽  
Author(s):  
Rujman Khan ◽  
Xin Yee Ooi ◽  
Matthew Parvus ◽  
Laura Valdez ◽  
Andrew Tsin
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Diabetic Complications ◽  
Tanshinone Iia ◽  
Future Research ◽  
Advanced Glycation ◽  
Reactive Aldehydes ◽  
Glycation End Products ◽  
End Products ◽  
Lysine Residues

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic retinopathy but will also explore how they impact other diseases.

scholarly journals Advanced Glycation End Products of Bovine Serum Albumin Suppressed Th1/Th2 Cytokine but Enhanced Monocyte IL-6 Gene Expression via MAPK-ERK and MyD88 Transduced NF-κB p50 Signaling Pathways

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2461 ◽  
Author(s):  
Chieh-Yu Shen ◽  
Cheng-Han Wu ◽  
Cheng-Hsun Lu ◽  
Yu-Min Kuo ◽  
Ko-Jen Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Advanced Glycation End Products ◽  
Binding Capacity ◽  
Carboxypeptidase Y ◽  
Functional Assay ◽  
Low Grade ◽  
Conformational Structure ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGE), the most known aging biomarker, may cause “inflamm-aging” (i.e., chronic low-grade inflammation that develops with aging) in both aged and diabetes groups. However, the molecular bases of inflamm-aging remain obscure. We prepared AGE by incubating BSA (0.0746 mmol/L) + glucose (0.5 mol/L) at 37 °C in 5% CO2–95% air for 1–180 days. The lysine glycation in BSA–AGE reached 77% on day 30 and 100% after day 130, whereas the glycation of arginine and cysteine was minimal. The Nε-(carboxymethyl)-lysine content in BSA–AGE was also increased with increasing number of incubation days. The lectin-binding assay revealed that the glycation of BSA not only altered the conformational structure, but lost binding capacity with various lectins. An immunological functional assay showed that BSA–AGE > 8 μg/mL significantly suppressed normal human Th1 (IL-2 and IFN-γ) and Th2 (IL-10) mRNA expression, whereas AGE > 0.5 μg/mL enhanced monocyte IL-6 production irrelevant to cell apoptosis. The AGE-enhanced monocyte IL-6 production was via MAPK–ERK and MyD88-transduced NF-κBp50 signaling pathways. To elucidate the structure–function relationship of BSA–AGE-enhanced IL-6 production, we pre-preincubated BSA–AGE with different carbohydrate-degrading, protein-degrading, and glycoprotein-degrading enzymes. We found that trypsin and carboxypeptidase Y suppressed whereas β-galactosidase enhanced monocyte IL-6 production. In conclusion, BSA–AGE exerted both immunosuppressive and pro-inflammatory effects that are the molecular basis of inflamm-aging in aged and diabetes groups.

scholarly journals Advanced Glycation End-Products in Skeletal Muscle Aging

2021 ◽  
Vol 8 (11) ◽  
pp. 168
Author(s):  
Lucas C. Olson ◽  
James T. Redden ◽  
Zvi Schwartz ◽  
David J. Cohen ◽  
Michael J. McClure
Keyword(s):  
Skeletal Muscle ◽  
Advanced Glycation End Products ◽  
Future Research ◽  
Cross Linking ◽  
Advanced Glycation ◽  
Muscle Aging ◽  
Glycation End Products ◽  
End Products ◽  
Skeletal Muscle Aging

Advanced age causes skeletal muscle to undergo deleterious changes including muscle atrophy, fast-to-slow muscle fiber transition, and an increase in collagenous material that culminates in the age-dependent muscle wasting disease known as sarcopenia. Advanced glycation end-products (AGEs) non-enzymatically accumulate on the muscular collagens in old age via the Maillard reaction, potentiating the accumulation of intramuscular collagen and stiffening the microenvironment through collagen cross-linking. This review contextualizes known aspects of skeletal muscle extracellular matrix (ECM) aging, especially the role of collagens and AGE cross-linking, and underpins the motor nerve’s role in this aging process. Specific directions for future research are also discussed, with the understudied role of AGEs in skeletal muscle aging highlighted. Despite more than a half century of research, the role that intramuscular collagen aggregation and cross-linking plays in sarcopenia is well accepted yet not well integrated with current knowledge of AGE’s effects on muscle physiology. Furthermore, the possible impact that motor nerve aging has on intramuscular cross-linking and muscular AGE levels is posited.

Sign in / Sign up

Export Citation Format

Share Document