scholarly journals Exposure of Caenorhabditis elegans to Dietary Nε-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4398
Author(s):  
Constance Dubois ◽  
Rachel Litke ◽  
Stéphane Rianha ◽  
Charles Paul-Constant ◽  
Jean-Marc Lo Guidice ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Intestinal Absorption ◽  
Advanced Glycation End Products ◽  
Peptide Transporter ◽  
Advanced Glycation ◽  
Pathophysiological Mechanisms ◽  
Glycation End Products ◽  
End Products ◽  
The Impact ◽  
Absorption Pathways

The impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free AGE adducts and transport of glycated di-tripeptides by the peptide transporter 1 (PEPT-1), are not compatible with certain pathophysiological processes described. To get new insight into the intestinal absorption pathways and the pathophysiological mechanisms of dAGEs, we initiated an in vivo study with a so-called simple animal model with a complete digestive tract, Caenorhabditis elegans. Dietary bacteria were chemically modified with glyoxylic acid to mainly produce Nε-carboxymethyllysine (CML) and used to feed the worms. We performed different immunotechniques using an anti-CML antibody for the relative quantification of ingested CML and localization of this AGE in the worms’ intestine. The relative expression of genes encoding different biological processes such as response to stresses and intestinal digestion were determined. The physiological development of the worms was verified. All the results were compared with those obtained with the control bacteria. The results revealed a new route for the intestinal absorption of dietary CML (dCML), endocytosis, which could be mediated by scavenger receptors. The exposure of worms to dCML induced a reproductive defect and a transcriptional response reflecting oxidative, carbonyl and protein folding stresses. These data, in particular the demonstration of endocytosis of dCML by enterocytes, open up new perspectives to better characterize the pathophysiological mechanisms of dAGEs.

Advanced glycation end products (AGEs) in metabolic disease: linking diet, inflammation and microbiota

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Giulia Gaudioso ◽  
Debora Collotta ◽  
Fausto Chiazza ◽  
Raffaella Mastrocola ◽  
Alessia Cento ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Gut Microbiota ◽  
Advanced Glycation End Products ◽  
Disease Risk ◽  
In Vivo Studies ◽  
Blood Levels ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
The Impact

AbstractIntroduction:High sugar consumption promotes endogenous formation of advanced glycation end-products (AGEs), a heterogeneous class of molecules originated from non-enzymatic glycation between reducing sugars and free amino groups of proteins, nucleic acids, or lipids. AGEs accumulation in tissues has been linked to aging and diabetes complications. AGEs might also play an independent role in inflammation and development of cardiovascular disease (CVD). Exogenous dietary AGEs, due to excess intake of modern heat-treated foods, might act synergistically with endogenous AGEs, thus contributing to increase inflammation and CVD. A large amount of ingested AGEs reaches the colon, where they might affect gut microbial metabolism, for example, by acting as substrate for colonic bacterial fermentation, driving alterations of microbiota composition and of intestinal permeability. However in vitro and in vivo studies (animal and human) on the impact of AGEs on the gut microbiota are discordant. This study on mice aims to link the modulation of gut microbiota by AGEs-enriched diet (AGE-D) with metabolic and inflammatory markers.Materials and methods:C57BL/6 mice were randomly allocated into the following dietary regimens: Control (n = 24) and AGE-D (n = 20) for 22 weeks. AGE-D was prepared replacing casein (200 g/kg diet) by an equal amount of modified casein where 10% of arginine was glycated with MG-H1 (methylglyoxal 5-hydro-5-methylimidazolone) for a total of 4 μmol of MG-H1 per g of diet. Faeces were collected using metabolic cages (18 h starving) at week 0, 11 and 22 for fecal DNA extraction and 16SrRNA analysis through Illumina MiSeq using V3-V4 targeted primers. After 22 weeks of dietary manipulation, mice were sacrificed, plasma and organ lipid profiles and serum metabolic and inflammatory profiles were determined.Results and discussion:AGE-D caused a significant reduction in the blood levels of two important components of the incretin system, GIP and GLP-1, when compared to control diet, suggestive of unbalance in the incretin-insulin axis. AGE-D exposure was associated with a significant increase in systemic concentrations of inflammatory cytokines, e.g. IL-1β and IL-17, and PAI-1, which has been suggested as both reliable marker and critical mediator of cellular senescence. We will present how AGEs impact on microbiome community structure and correlate changes in gut microbiota with GIP and GLP-1 levels.Conclusions:AGEs, characteristic of modern processed foods, appear to impact on the incretin-insulin axis, a key regulator of metabolic disease risk. Diets rich in AGEs may mediate these physiological effects at least in part, by reshaping intestinal microbiota structure.

scholarly journals Dietary Advanced Glycation End Products: Digestion, Metabolism and Modulation of Gut Microbial Ecology

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 215 ◽  
Author(s):  
Matthew Snelson ◽  
Melinda Coughlan
Keyword(s):  
Gut Microbiota ◽  
Advanced Glycation End Products ◽  
Short Chain Fatty Acids ◽  
Current Evidence ◽  
Advanced Glycation ◽  
Conflicting Evidence ◽  
Glycation End Products ◽  
End Products ◽  
Pass Through ◽  
The Impact

The formation of advanced glycation end products (AGEs) in foods is accelerated with heat treatment, particularly within foods that are cooked at high temperatures for long periods of time using dry heat. The modern processed diet is replete with AGEs, and excessive AGE consumption is thought to be associated with a number of negative health effects. Many dietary AGEs have high molecular weight and are not absorbed in the intestine, and instead pass through to the colon, where they are available for metabolism by the colonic bacteria. Recent studies have been conducted to explore the effects of AGEs on the composition of the gut microbiota as well as the production of beneficial microbial metabolites, in particular, short-chain fatty acids. However, there is conflicting evidence regarding the impact of dietary AGEs on gut microbiota reshaping, which may be due, in part, to the formation of alternate compounds during the thermal treatment of foods. This review summarises the current evidence regarding dietary sources of AGEs, their gastrointestinal absorption and role in gut microbiota reshaping, provides a brief overview of the health implications of dietary AGEs and highlights knowledge gaps and avenues for future study.

scholarly journals Examining the Role of Dietary Advanced Gycation End Products in Prostate Cancer Using Molecular Imaging Techniques (OR04-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Christian Konopka ◽  
Annaliese Paton ◽  
Aleksandra Skokowska ◽  
Joe Rowles ◽  
John Erdman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Serum Albumin ◽  
Advanced Glycation End Products ◽  
Growth Media ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
The Impact

Abstract Objectives The Receptor for Advanced Glycation End Products (RAGE) and its ligands have been shown to be both over expressed and critical to prostate cancer (PCa) development. Importantly, the overexpression of both RAGE and its ligands is associated with poor PCa patient survival, suggesting its promise as a molecular target. Additionally, one of the largest sources of ligands for RAGE, advanced glycation end products (AGEs), come from one's diet and their concentrations are directly related to disease. We hypothesized that dietary AGEs (dAGEs) significantly contribute to the progression of PCa through interactions with RAGE. In this study we explore the use of a novel imaging strategy targeted at RAGE in combination with conventional imaging and histological techniques to assess the role of dAGEs on RAGE expression and PCa progression in murine xenografts. Methods To examine the impact of AGEs on PCa cell function, experiments were performed in two PCa cell lines. Cells were grown in growth media enriched with carboxymethyl-lysine-modified human serum albumin (CML) (the most common AGE) or a control protein, bovine serum albumin (BSA). Western blot, confocal microscopy, clonogenic assays, and proliferations assays were performed. To study the effects of an enhanced consumption of dAGEs on PCa growth and progression in vivo, NU/J mice were fed a modified Ain-93 G diet, which was either CML or BSA enriched. PCa tumors were then initiated. Their growth was monitored, their perfusion measured using Speckle Contrast Imaging, and their metabolic rate and RAGE content quantified using 18FDG and a novel RAGE-targeted tracer using PET-CT. Finally, the tissues were excised for histological analysis. Results CML significantly enhanced in vitro expression of both RAGE and proliferation marker KI-67. Cell doubling time was also significantly quickened, (1.5 vs 2.4 days) in the CML vs control. In vivo data demonstrated significant differences in tumor growth (CML group up to 2-fold increase) and successful tumor implantation rate (30% vs 60%). Perfusion, metabolism, and RAGE imaging demonstrated unique patterns which varied over the course of PCa progression. Conclusions These studies indicate that dAGEs may play a significant role in the progression of PCa. The data suggests that RAGE and its ligands are promising targets for further therapeutic investigations. Funding Sources University of Illinois at Chicago Cancer Center Pilot Grant. Supporting Tables, Images and/or Graphs

scholarly journals Effects of Exogenous Dietary Advanced Glycation End Products on the Cross-Talk Mechanisms Linking Microbiota to Metabolic Inflammation

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2497
Author(s):  
Raffaella Mastrocola ◽  
Debora Collotta ◽  
Giulia Gaudioso ◽  
Marie Le Berre ◽  
Alessia Sofia Cento ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Protein Glycosylation ◽  
Advanced Glycation ◽  
Microbial Composition ◽  
Glycosylation Profile ◽  
Metabolic Inflammation ◽  
Altered Glucose ◽  
Glycation End Products ◽  
End Products ◽  
The Impact

Heat-processed diets contain high amounts of advanced glycation end products (AGEs). Here we explore the impact of an AGE-enriched diet on markers of metabolic and inflammatory disorders as well as on gut microbiota composition and plasma proteins glycosylation pattern. C57BL/6 mice were allocated into control diet (CD, n = 15) and AGE-enriched diet (AGE-D, n = 15) for 22 weeks. AGE-D was prepared replacing casein by methylglyoxal hydroimidazolone-modified casein. AGE-D evoked increased insulin and a significant reduction of GIP/GLP-1 incretins and ghrelin plasma levels, altered glucose tolerance, and impaired insulin signaling transduction in the skeletal muscle. Moreover, AGE-D modified the systemic glycosylation profile, as analyzed by lectin microarray, and increased Nε-carboxymethyllysine immunoreactivity and AGEs receptor levels in ileum and submandibular glands. These effects were associated to increased systemic levels of cytokines and impaired gut microbial composition and homeostasis. Significant correlations were recorded between changes in bacterial population and in incretins and inflammatory markers levels. Overall, our data indicates that chronic exposure to dietary AGEs lead to a significant unbalance in incretins axis, markers of metabolic inflammation, and a reshape of both the intestinal microbiota and plasma protein glycosylation profile, suggesting intriguing pathological mechanisms underlying AGEs-induced metabolic derangements.

The impact of resveratrol on toxicity and related complications of advanced glycation end products: A systematic review

BioFactors ◽  
2019 ◽  
Vol 45 (5) ◽  
pp. 651-665 ◽  
Author(s):  
Fatemeh Hajizadeh‐Sharafabad ◽  
Amirhossein Sahebkar ◽  
Fateme Zabetian‐Targhi ◽  
Vahid Maleki
Keyword(s):  
Systematic Review ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
The Impact

scholarly journals Autofluorescence as a noninvasive biomarker of senescence and advanced glycation end products in Caenorhabditis elegans

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tomomi Komura ◽  
Mikihiro Yamanaka ◽  
Kohji Nishimura ◽  
Keita Hara ◽  
Yoshikazu Nishikawa
Keyword(s):  
Caenorhabditis Elegans ◽  
Advanced Glycation End Products ◽  
Fluorescence Intensity ◽  
High Resolution Mass Spectrometry ◽  
Age Factors ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Noninvasive Biomarker

AbstractTo assess the utility of autofluorescence as a noninvasive biomarker of senescence in Caenorhabditis elegans, we measured the autofluorescence of individual nematodes using spectrofluorometry. The fluorescence of each worm increased with age. Animals with lower fluorescence intensity exhibited longer life expectancy. When proteins extracted from worms were incubated with sugars, the fluorescence intensity and the concentration of advanced glycation end products (AGEs) increased over time. Ribose enhanced these changes not only in vitro but also in vivo. The glycation blocker rifampicin suppressed this rise in fluorescence. High-resolution mass spectrometry revealed that vitellogenins accumulated in old worms, and glycated vitellogenins emitted six-fold higher fluorescence than naive vitellogenins. The increase in fluorescence with ageing originates from glycated substances, and therefore could serve as a useful noninvasive biomarker of AGEs. C. elegans can serve as a new model to look for anti-AGE factors and to study the relationship between AGEs and senescence.

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