Nutrients

Research

14 pages, 1486 KiB

Open AccessArticle

Advanced Glycation End Products (AGEs) in Diet and Skin in Relation to Stool Microbiota: The Rotterdam Study

by Jinluan Chen, Djawad Radjabzadeh, Carolina Medina-Gomez, Trudy Voortman, Joyce B. J. van Meurs, M. Arfan Ikram, André G. Uitterlinden, Robert Kraaij and M. Carola Zillikens

Nutrients 2023, 15(11), 2567; https://doi.org/10.3390/nu15112567 - 30 May 2023

Cited by 7 | Viewed by 2036

Abstract

Background: Advanced glycation end products (AGEs) are involved in age-related diseases, but the interaction of gut microbiota with dietary AGEs (dAGEs) and tissue AGEs in the population is unknown. Objective: Our objective was to investigate the association of dietary and tissue AGEs with [...] Read more.

Background: Advanced glycation end products (AGEs) are involved in age-related diseases, but the interaction of gut microbiota with dietary AGEs (dAGEs) and tissue AGEs in the population is unknown. Objective: Our objective was to investigate the association of dietary and tissue AGEs with gut microbiota in the population-based Rotterdam Study, using skin AGEs as a marker for tissue accumulation and stool microbiota as a surrogate for gut microbiota. Design: Dietary intake of three AGEs (dAGEs), namely carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL), was quantified at baseline from food frequency questionnaires. Following up after a median of 5.7 years, skin AGEs were measured using skin autofluorescence (SAF), and stool microbiota samples were sequenced (16S rRNA) to measure microbial composition (including alpha-diversity, beta-dissimilarity, and taxonomic abundances) as well as predict microbial metabolic pathways. Associations of both dAGEs and SAF with microbial measures were investigated using multiple linear regression models in 1052 and 718 participants, respectively. Results: dAGEs and SAF were not associated with either the alpha-diversity or beta-dissimilarity of the stool microbiota. After multiple-testing correction, dAGEs were not associated with any of the 188 genera tested, but were nominally inversely associated with the abundance of Barnesiella, Colidextribacter, Oscillospiraceae UCG-005, and Terrisporobacter, in addition to being positively associated with Coprococcus, Dorea, and Blautia. A higher abundance of Lactobacillus was associated with a higher SAF, along with several nominally significantly associated genera. dAGEs and SAF were nominally associated with several microbial pathways, but none were statistically significant after multiple-testing correction. Conclusions: Our findings did not solidify a link between habitual dAGEs, skin AGEs, and overall stool microbiota composition. Nominally significant associations with several genera and functional pathways suggested a potential interaction between gut microbiota and AGE metabolism, but validation is required. Future studies are warranted, to investigate whether gut microbiota modifies the potential impact of dAGEs on health. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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12 pages, 1961 KiB

Open AccessArticle

Skin Autofluorescence Mirrors Surrogate Parameters of Vascular Aging: An Enable Study

by Tianxing Du, Beate Brandl, Hans Hauner and Thomas Skurk

Nutrients 2023, 15(7), 1597; https://doi.org/10.3390/nu15071597 - 25 Mar 2023

Cited by 2 | Viewed by 2069

Abstract

Advanced glycation end-products (AGEs) are implicated in vascular aging due to their pro-inflammatory properties. Skin autofluorescence (SAF) is a measure to estimate their deposition. It is an easily quantifiable marker that has been shown to correlate with cardiovascular risk and parameters of metabolic [...] Read more.

Advanced glycation end-products (AGEs) are implicated in vascular aging due to their pro-inflammatory properties. Skin autofluorescence (SAF) is a measure to estimate their deposition. It is an easily quantifiable marker that has been shown to correlate with cardiovascular risk and parameters of metabolic diseases. Herein, we compared skin autofluorescence with other techniques indicating increased cardiovascular diseases, namely, pulse wave velocity (PWVao) and intima–media thickness (IMT). We also studied the impacts of other parameters in deeply phenotyped cohorts of young, middle-aged, and older individuals. SAF, aortic PWVao, and IMT proved to be significantly correlated with each other and with age. However, based on a moderator analysis, we could not show that these associations were affected by age. Some specific parameters such as creatinine and CRP were found to be significantly associated with skin AGE values after adjusting for confounding variables. In conclusion, SAF is a simple screening tool for vascular health with comparable power to more elaborated technical tests. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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13 pages, 1259 KiB

Open AccessArticle

Alcoholic Liver Disease Is Associated with Elevated Plasma Levels of Novel Advanced Glycation End-Products: A Preliminary Study

by Kamil Litwinowicz, Ewa Waszczuk, Aleksandra Kuzan, Agnieszka Bronowicka-Szydełko, Kinga Gostomska-Pampuch, Piotr Naporowski and Andrzej Gamian

Nutrients 2022, 14(24), 5266; https://doi.org/10.3390/nu14245266 - 10 Dec 2022

Cited by 4 | Viewed by 2381

Abstract

Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver [...] Read more.

Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver injuries. Recently, we determined the structure of a synthetic, melibiose-derived AGE (MAGE), which was an analog of the novel AGE subgroup AGE10. The primary objective of our study was to determine whether AGE10 was associated with alcoholic hepatitis. The secondary objective was to provide a diagnostic accuracy of AGE10 in AH. To achieve this objective, we examined the plasma levels of AGE10 in 65 healthy individuals and 65 patients with AH. The AGE10 level was measured using a competitive ELISA. Our study confirmed that patients with AH had significantly higher plasma concentrations of AGE10 compared with healthy controls (184.5 ± 71.1 μg/mL and 123.5 ± 44.9 μg/mL, respectively; p < 0.001). In addition, AGE10 showed an acceptable performance as a diagnostic marker of AH, with an AUC of 0.78. In conclusion, AH was associated with elevated levels of novel advanced glycation end-product AGE10. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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14 pages, 344 KiB

Open AccessArticle

Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study

by Melinda Csongová, Jean L. J. M. Scheijen, Marjo P. H. van de Waarenburg, Radana Gurecká, Ivana Koborová, Tamás Tábi, Éva Szökö, Casper G. Schalkwijk and Katarína Šebeková

Nutrients 2022, 14(22), 4929; https://doi.org/10.3390/nu14224929 - 21 Nov 2022

Cited by 6 | Viewed by 1999

Abstract

α-Dicarbonyls and advanced glycation end products (AGEs) may contribute to the pathogenesis of insulin resistance by a variety of mechanisms. To investigate whether young insulin-resistant subjects present markers of increased dicarbonyl stress, we determined serum α-dicarbonyls-methylglyoxal, glyoxal, 3-deoxyglucosone; their derived free- and protein-bound, [...] Read more.

α-Dicarbonyls and advanced glycation end products (AGEs) may contribute to the pathogenesis of insulin resistance by a variety of mechanisms. To investigate whether young insulin-resistant subjects present markers of increased dicarbonyl stress, we determined serum α-dicarbonyls-methylglyoxal, glyoxal, 3-deoxyglucosone; their derived free- and protein-bound, and urinary AGEs using the UPLC/MS-MS method; soluble receptors for AGEs (sRAGE), and cardiometabolic risk markers in 142 (49% females) insulin resistant (Quantitative Insulin Sensitivity Check Index (QUICKI) ≤ 0.319) and 167 (47% females) age-, and waist-to-height ratio-matched insulin-sensitive controls aged 16-to-22 years. The between-group comparison was performed using the two-factor (sex, presence/absence of insulin resistance) analysis of variance; multiple regression via the orthogonal projection to latent structures model. In comparison with their insulin-sensitive peers, young healthy insulin-resistant individuals without diabetes manifest alterations throughout the α-dicarbonyls-AGEs-sRAGE axis, dominated by higher 3-deoxyglucosone levels. Variables of α-dicarbonyls-AGEs-sRAGE axis were associated with insulin sensitivity independently from cardiometabolic risk markers, and sex-specifically. Cleaved RAGE associates with QUICKI only in males; while multiple α-dicarbonyls and AGEs independently associate with QUICKI particularly in females, who displayed a more advantageous cardiometabolic profile compared with males. Further studies are needed to elucidate whether interventions alleviating dicarbonyl stress ameliorate insulin resistance. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

15 pages, 4401 KiB

Open AccessArticle

Rye Bread Crust as an Inducer of Antioxidant Genes and Suppressor of NF-κB Pathway In Vivo

by Kristin Wächter, Birte Gohde, Gábor Szabó and Andreas Simm

Nutrients 2022, 14(22), 4790; https://doi.org/10.3390/nu14224790 - 12 Nov 2022

Cited by 3 | Viewed by 1923

Abstract

Heat-processed food, like bread, containing high amounts of advanced glycation end products (AGEs), is controversially discussed regarding the effects on health and disease. In in vitro and in vivo experiments, AGEs can induce proinflammatory NF-κB and/or the anti-inflammatory NRF2 pathways. The aim of [...] Read more.

Heat-processed food, like bread, containing high amounts of advanced glycation end products (AGEs), is controversially discussed regarding the effects on health and disease. In in vitro and in vivo experiments, AGEs can induce proinflammatory NF-κB and/or the anti-inflammatory NRF2 pathways. The aim of this study was to investigate how gene expression is influenced in vivo upon short as well as long-term feeding of mice with control and bread crust-food (BC). For that, the liver, kidney and heart from two days- and eight days-fed mice were isolated and gene arrays were performed. Fewer genes were affected in terms of expression after two days of BC feeding than after eight days. We observed, especially in the heart and to lesser extent in the liver, an induction of antioxidant response by BC. Among the significantly up-regulated genes identified in the heart were transcripts encoding for cardioprotective and antioxidative proteins like metallothionein 2, uncoupling protein 3 and pyruvate dehydrogenase kinase 4. In contrast, in the liver, genes encoding for inflammatory drivers like thioredoxin-interacting protein, lncRNA Mtss1 and ubiquitin-specific protease 2 were down-modulated. However, an increased expression of immunoglobulins was observed in the kidney. Furthermore, in vivo imaging analyses with NF-κB-luciferase-reporter mice uncovered a rather anti-inflammatory response, especially after three and seven days of the feeding study. Our results suggest that bread crust exerts antioxidant and anti-inflammatory effects in the model organism mouse in an organ-specific manner. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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10 pages, 510 KiB

Open AccessArticle

Association between Urinary Advanced Glycation End Products and Subclinical Inflammation in Children and Adolescents: Results from the Italian I.Family Cohort

by Margherita Borriello, Fabio Lauria, Ivana Sirangelo, Krasimira Aleksandrova, Antje Hebestreit, Alfonso Siani and Paola Russo

Nutrients 2022, 14(19), 4135; https://doi.org/10.3390/nu14194135 - 5 Oct 2022

Cited by 2 | Viewed by 1799

Abstract

Advanced Glycation End Products (AGEs) have been positively correlated with inflammation in adults, while inconsistent evidence is available in children. We evaluated the association between urinary AGEs, measured by fluorescence spectroscopy, and biomarkers of subclinical inflammation in 676 healthy children/adolescents (age 11.8 ± [...] Read more.

Advanced Glycation End Products (AGEs) have been positively correlated with inflammation in adults, while inconsistent evidence is available in children. We evaluated the association between urinary AGEs, measured by fluorescence spectroscopy, and biomarkers of subclinical inflammation in 676 healthy children/adolescents (age 11.8 ± 1.6 years, M ± SD) from the Italian cohort of the I.Family project. Urinary fluorescent AGEs were used as independent variable and high-sensitivity C-reactive protein (hs-CRP) was the primary outcome, while other biomarkers of inflammation were investigated as secondary outcomes. Participants with urinary AGEs above the median of the study population showed statistically significantly higher hs-CRP levels as compared to those below the median (hs-CRP 0.44 ± 1.1 vs. 0.24 ± 0.6 mg/dL, M ± SD p = 0.002). We found significant positive correlations between urinary AGEs and hs-CRP (p = 0.0001), IL-15 (p = 0.001), IP-10 (p = 0.006), and IL-1Ra (p = 0.001). At multiple regression analysis, urinary AGEs, age, and BMI Z-score were independent variables predicting hs-CRP levels. We demonstrated for the first time, in a large cohort of children and adolescents, that the measurement of fluorescent urinary AGEs may represent a simple, noninvasive, and rapid technique to evaluate the association between AGEs and biomarkers of inflammation. Our data support a role of AGEs as biomarkers of subclinical inflammation in otherwise healthy children and adolescents. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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10 pages, 1001 KiB

Open AccessArticle

Studies on the Reaction of Dietary Methylglyoxal and Creatine during Simulated Gastrointestinal Digestion and in Human Volunteers

by Stephanie Treibmann, Julia Groß, Susann Pätzold and Thomas Henle

Nutrients 2022, 14(17), 3598; https://doi.org/10.3390/nu14173598 - 31 Aug 2022

Cited by 8 | Viewed by 2068

Abstract

The reactive 1,2-dicarbonyl compound methylglyoxal (MGO) is consumed with food and its concentrations decrease during digestion. In the present paper, the reaction of MGO with creatine, arginine, and lysine during simulated digestion, and its reaction with creatine during the digestion in human volunteers, [...] Read more.

The reactive 1,2-dicarbonyl compound methylglyoxal (MGO) is consumed with food and its concentrations decrease during digestion. In the present paper, the reaction of MGO with creatine, arginine, and lysine during simulated digestion, and its reaction with creatine during the digestion in human volunteers, was studied. Therefore, simulated digestion experiments with a gastric and an intestinal phase were performed. Additionally, an intervention study with 12 subjects consuming MGO-containing Manuka honey and creatine simultaneously or separately was conducted. Derivatization with o-phenylenediamine and HPLC–UV was used to measure MGO, while creatine and glycated amino compounds were analyzed via HPLC–MS/MS. We show that MGO quickly reacts with creatine and arginine, but not lysine, during simulated digestion. Creatine reacts with 56% of MGO to form the hydroimidazolone MG-HCr, and arginine reacted with 4% of MGO to form the hydroimidazolone MG-H1. In the intervention study, urinary MG-HCr excretion is higher in subjects who consumed MGO and creatine simultaneously compared to subjects who ingested the substances separately. This demonstrates that the 1,2-dicarbonyl compound MGO reacts with amino compounds during human digestion, and glycated adducts are formed. These contribute to dietary glycation products consumed, and should be considered in studies investigating their physiological consequences. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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16 pages, 1657 KiB

Open AccessArticle

Plasma Levels of Free N^Ɛ-Carboxymethyllysine (CML) after Different Oral Doses of CML in Rats and after the Intake of Different Breakfasts in Humans: Postprandial Plasma Level of sRAGE in Humans

by Cynthia Helou, Matheus Thomaz Nogueira Silva Lima, Céline Niquet-Leridon, Philippe Jacolot, Eric Boulanger, Florian Delguste, Axel Guilbaud, Michael Genin, Pauline M. Anton, Carine Delayre-Orthez, Tatiana Papazian, Michael Howsam and Frédéric J. Tessier

Nutrients 2022, 14(9), 1890; https://doi.org/10.3390/nu14091890 - 30 Apr 2022

Cited by 9 | Viewed by 2431

Abstract

N-carboxymethyl-lysine (CML) and other dietary advanced glycation end-products (AGEs) are chemically modified amino acids with potential toxicological effects putatively related to their affinity with the receptor for AGEs (RAGE). The goal of this study was to determine the postprandial kinetics of CML in [...] Read more.

N-carboxymethyl-lysine (CML) and other dietary advanced glycation end-products (AGEs) are chemically modified amino acids with potential toxicological effects putatively related to their affinity with the receptor for AGEs (RAGE). The goal of this study was to determine the postprandial kinetics of CML in both rodents and humans and, in the latter, to evaluate their relationship with the soluble RAGE isoforms (sRAGE). Four gavage solutions containing different forms of CML were given to rats, and blood was collected over 8 h. Three different breakfasts containing dietary CML (dCML) were administered to 20 healthy volunteers, and blood was collected over 2 h. Concentrations of CML, CEL, and lysine were quantified in plasma and human meals by LC-MS/MS, and sRAGE was determined in human plasma by ELISA. The results showed that dCML did not affect the concentrations of circulating protein-bound CML and that only free CML increased in plasma, with a postprandial peak at 90 to 120 min. In humans, the postprandial plasmatic sRAGE concentration decreased independently of the dAGE content of the breakfasts. This study confirms reports of the inverse postprandial relationship between plasmatic free CML and sRAGE, though this requires further investigation for causality to be established. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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11 pages, 548 KiB

Open AccessArticle

Dietary Advanced Glycation End Products in an Elderly Population with Diabetic Nephropathy: An Exploratory Investigation

by Mieke Steenbeke, Ignace De Decker, Sophie Marchand, Griet Glorieux, Wim Van Biesen, Bruno Lapauw, Joris R. Delanghe and Marijn M. Speeckaert

Nutrients 2022, 14(9), 1818; https://doi.org/10.3390/nu14091818 - 27 Apr 2022

Cited by 10 | Viewed by 2708

Abstract

Advanced glycation end products (AGEs) are important in pathophysiology of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Dietary AGEs (dAGEs) contribute to the overall AGE pool in the body. Forty elderly T2DM patients with DKD were randomly allocated to a [...] Read more.

Advanced glycation end products (AGEs) are important in pathophysiology of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Dietary AGEs (dAGEs) contribute to the overall AGE pool in the body. Forty elderly T2DM patients with DKD were randomly allocated to a low-AGE (n = 20) or regular diabetic (n = 20) diet group. A three-day meal questionnaire was used to estimate average quantity of dAGEs. AGE accumulation was measured using skin autofluorescence and urine spectroscopy. sRAGE (soluble receptor AGE) was quantified using ELISA. After 8 weeks, the mean consumption of dAGEs was considerably reduced, both in the low-AGE diet (p = 0.004) and the control (p = 0.019) group. The expected urinary emission peak at 490 nm was shifted to 520 nm in some spectra. dAGEs did not correspond with urine AGE output. An AGE-limited diet for two months did not affect AGE content in skin and urine, or sRAGE concentration in the blood. The role of glycemia is likely to be greater than the impact of dAGE consumption. The unique observation of a fluorescence pattern at 520 nm warrants further examination, since it might point to genetic differences in AGE regulation, which could have clinical consequences, as AGE content depends on its formation and elimination. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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16 pages, 3784 KiB

Open AccessArticle

The Influence of Intracellular Glutathione Levels on the Induction of Nrf2-Mediated Gene Expression by α-Dicarbonyl Precursors of Advanced Glycation End Products

by Liang Zheng, Katja C. W. van Dongen, Wouter Bakker, Ignacio Miro Estruch and Ivonne M. C. M. Rietjens

Nutrients 2022, 14(7), 1364; https://doi.org/10.3390/nu14071364 - 24 Mar 2022

Cited by 11 | Viewed by 2829

Abstract

α-Dicarbonyl compounds, particularly methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), are highly reactive precursors for the formation of advanced glycation end products (AGEs). They are formed in vivo and during food processing. This study aimed to investigate the role of intracellular glutathione (GSH) [...] Read more.

α-Dicarbonyl compounds, particularly methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), are highly reactive precursors for the formation of advanced glycation end products (AGEs). They are formed in vivo and during food processing. This study aimed to investigate the role of intracellular glutathione (GSH) levels in the induction of Nrf2-mediated gene expression by α-dicarbonyl compounds. The reactions between α-dicarbonyl compounds (MGO, GO, and 3-DG) and GSH were studied by LC-MS in a cell-free system. It was shown that these three α-dicarbonyl compounds react instantaneously with GSH, with the GSH-mediated scavenging decreasing in the order MGO > GO > 3DG. Furthermore, in a cell-based reporter gene assay MGO, GO, and 3-DG were able to induce Nrf2-mediated gene expression in a dose-dependent manner. Modulation of intracellular GSH levels showed that the cytotoxicity and induction of the Nrf2-mediated pathway by MGO, GO and 3-DG was significantly enhanced by depletion of GSH, while a decrease in Nrf2-activation by MGO and GO but not 3-DG was observed upon an increase of the cellular GSH levels. Our results reveal subtle differences in the role of GSH in protection against the three typical α-dicarbonyl compounds and in their induction of Nrf2-mediated gene expression, and point at a dual biological effect of the α-dicarbonyl compounds, being reactive toxic electrophiles and -as a consequence- able to induce Nrf2-mediated protective gene expression, with MGO being most reactive. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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8 pages, 1043 KiB

Open AccessArticle

Weak Association between Skin Autofluorescence Levels and Prediabetes with an ILERVAS Cross-Sectional Study

by Enric Sánchez, Mohsen Kerkeni, Marta Hernández, Ricard Gavaldà, Ferran Rius, Ariadna Sauret, Gerard Torres, Marcelino Bermúdez-López, Elvira Fernández, Eva Castro-Boqué, Francisco Purroy, Dídac Mauricio, Cristina Farràs-Sallés, Miquel Buti, Pere Godoy, Reinald Pamplona and Albert Lecube

Nutrients 2022, 14(5), 1102; https://doi.org/10.3390/nu14051102 - 5 Mar 2022

Viewed by 2515

Abstract

A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of [...] Read more.

A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of prediabetes is unclear. A cross-sectional study was conducted in 4181 middle-aged subjects without diabetes. Prediabetes (n = 1444) was defined as a glycosylated hemoglobin (HbA1c) level between 39 and 47 mmol/mol (5.7 to 6.4%), and skin autofluorescence (SAF) measurement was performed to assess AGEs. A multivariable logistic regression model and receiver operating characteristic curve were used. The cohort consisted of 50.1% women with an age of 57 [52;62] years, a BMI of 28.3 [25.4;31.6] kg/m², and a prevalence of prediabetes of 34.5%. Participants with prediabetes showed higher SAF than control participants (2.0 [1.7;2.2] vs. 1.9 [1.7;2.2], p < 0.001). However, HbA1c was not significantly correlated with SAF levels (r = 0.026, p = 0.090). In addition, the SAF level was not independently associated with prediabetes (OR = 1.12 (0.96 to 1.30)). Finally, there was no good cutoff point for SAF to identify patients with prediabetes (AUC = 0.52 (0.50 to 0.54), sensitivity = 0.61, and 1-specificity = 0.56). Given all of this evidence, we can conclude that although there is an increase in SAF levels in participants with prediabetes, the applicability and clinical relevance of the results is low in this population. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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19 pages, 6803 KiB

Open AccessArticle

Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress

by Evelyn Nunes Goulart da Silva Pereira, Beatriz Peres de Araujo, Karine Lino Rodrigues, Raquel Rangel Silvares, Carolina Souza Machado Martins, Edgar Eduardo Ilaquita Flores, Caroline Fernandes-Santos and Anissa Daliry

Nutrients 2022, 14(3), 716; https://doi.org/10.3390/nu14030716 - 8 Feb 2022

Cited by 21 | Viewed by 3818

Abstract

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver [...] Read more.

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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14 pages, 1816 KiB

Open AccessArticle

Dietary Intake of Advanced Glycation End Products (AGEs) and Mortality among Individuals with Colorectal Cancer

by Ziling Mao, Elom K. Aglago, Zhiwei Zhao, Casper Schalkwijk, Li Jiao, Heinz Freisling, Elisabete Weiderpass, David J. Hughes, Anne Kirstine Eriksen, Anne Tjønneland, Gianluca Severi, Joseph Rothwell, Marie-Christine Boutron-Ruault, Verena Katzke, Rudolf Kaaks, Matthias B. Schulze, Anna Birukov, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Roel C. H. Vermeulen, Inger T. Gram, Guri Skeie, Torkjel M. Sandanger, J. Ramón Quirós, Marta Crous-Bou, Maria-Jose Sánchez, Pilar Amiano, María-Dolores Chirlaque, Aurelio Barricarte Gurrea, Jonas Manjer, Ingegerd Johansson, Aurora Perez-Cornago, Mazda Jenab and Veronika Fedirko Show full author list Hide full author list

Nutrients 2021, 13(12), 4435; https://doi.org/10.3390/nu13124435 - 10 Dec 2021

Cited by 11 | Viewed by 5529

Abstract

Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were [...] Read more.

Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, P_interaction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, P_interaction = 0.003; all-cause, P_interaction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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Review

Jump to: Research, Other

20 pages, 857 KiB

Open AccessReview

Blood and Tissue Advanced Glycation End Products as Determinants of Cardiometabolic Disorders Focusing on Human Studies

by Yoona Kim

Nutrients 2023, 15(8), 2002; https://doi.org/10.3390/nu15082002 - 21 Apr 2023

Cited by 5 | Viewed by 2966

Abstract

Cardiometabolic disorders are characterised by a cluster of interactive risk determinants such as increases in blood glucose, lipids and body weight, as well as elevated inflammation and oxidative stress and gut microbiome changes. These disorders are associated with onset of type 2 diabetes [...] Read more.

Cardiometabolic disorders are characterised by a cluster of interactive risk determinants such as increases in blood glucose, lipids and body weight, as well as elevated inflammation and oxidative stress and gut microbiome changes. These disorders are associated with onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). T2DM is strongly associated with CVD. Dietary advanced glycation end products (dAGEs) attributable from modern diets high in sugar and/or fat, highly processed foods and high heat-treated foods can contribute to metabolic etiologies of cardiometabolic disorders. This mini review aims to determine whether blood dAGEs levels and tissue dAGEs levels are determinants of the prevalence of cardiometabolic disorders through recent human studies. ELISA (enzyme-linked immunosorbent assay), high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) for blood dAGEs measurement and skin auto fluorescence (SAF) for skin AGEs measurement can be used. Recent human studies support that a diet high in AGEs can negatively influence glucose control, body weight, blood lipid levels and vascular health through the elevated oxidative stress, inflammation, blood pressure and endothelial dysfunction compared with a diet low in AGEs. Limited human studies suggested a diet high in AGEs could negatively alter gut microbiota. SAF could be considered as one of the predictors affecting risks for cardiometabolic disorders. More intervention studies are needed to determine how dAGEs are associated with the prevalence of cardiometabolic disorders through gut microbiota changes. Further human studies are conducted to find the association between CVD events, CVD mortality and total mortality through SAF measurement, and a consensus on whether tissue dAGEs act as a predictor of CVD is required. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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17 pages, 1138 KiB

Open AccessEditor’s ChoiceReview

Advanced Glycation End-Products and Their Effects on Gut Health

by Kate Phuong-Nguyen, Bryony A. McNeill, Kathryn Aston-Mourney and Leni R. Rivera

Nutrients 2023, 15(2), 405; https://doi.org/10.3390/nu15020405 - 13 Jan 2023

Cited by 31 | Viewed by 6087

Abstract

Dietary advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed when reducing sugars are heated with proteins, amino acids, or lipids at high temperatures for a prolonged period. The presence and accumulation of AGEs in numerous cell types and tissues are [...] Read more.

Dietary advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed when reducing sugars are heated with proteins, amino acids, or lipids at high temperatures for a prolonged period. The presence and accumulation of AGEs in numerous cell types and tissues are known to be prevalent in the pathology of many diseases. Modern diets, which contain a high proportion of processed foods and therefore a high level of AGE, cause deleterious effects leading to a multitude of unregulated intracellular and extracellular signalling and inflammatory pathways. Currently, many studies focus on investigating the chemical and structural aspects of AGEs and how they affect the metabolism and the cardiovascular and renal systems. Studies have also shown that AGEs affect the digestive system. However, there is no complete picture of the implication of AGEs in this area. The gastrointestinal tract is not only the first and principal site for the digestion and absorption of dietary AGEs but also one of the most susceptible organs to AGEs, which may exert many local and systemic effects. In this review, we summarise the current evidence of the association between a high-AGE diet and poor health outcomes, with a special focus on the relationship between dietary AGEs and alterations in the gastrointestinal structure, modifications in enteric neurons, and microbiota reshaping. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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17 pages, 1472 KiB

Open AccessEditor’s ChoiceReview

Accumulation of Advanced Glycation End-Products in the Body and Dietary Habits

by Agnieszka Zawada, Alicja Machowiak, Anna Maria Rychter, Alicja Ewa Ratajczak, Aleksandra Szymczak-Tomczak, Agnieszka Dobrowolska and Iwona Krela-Kaźmierczak

Nutrients 2022, 14(19), 3982; https://doi.org/10.3390/nu14193982 - 25 Sep 2022

Cited by 30 | Viewed by 6157

Abstract

The formation of advanced glycation end-products (AGE) in tissues is a physiological process; however, excessive production and storage are pathological and lead to inflammation. A sedentary lifestyle, hypercaloric and high-fructose diet and increased intake of processed food elements contribute to excessive production of [...] Read more.

The formation of advanced glycation end-products (AGE) in tissues is a physiological process; however, excessive production and storage are pathological and lead to inflammation. A sedentary lifestyle, hypercaloric and high-fructose diet and increased intake of processed food elements contribute to excessive production of compounds, which are created in the non-enzymatic multi-stage glycation process. The AGE’s sources can be endogenous and exogenous, mainly due to processing food at high temperatures and low moisture, including grilling, roasting, and frying. Accumulation of AGE increases oxidative stress and initiates various disorders, leading to the progression of atherosclerosis, cardiovascular disease, diabetes and their complications. Inborn defensive mechanisms, recovery systems, and exogenous antioxidants (including polyphenols) protect from excessive AGE accumulation. Additionally, numerous products have anti-glycation properties, occurring mainly in fruits, vegetables, herbs, and spices. It confirms the role of diet in the prevention of civilization diseases. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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12 pages, 493 KiB

Open AccessReview

Contribution of Advanced Glycation End Products to PCOS Key Elements: A Narrative Review

by Marco Mouanness, Henry Nava, Christelle Dagher and Zaher Merhi

Nutrients 2022, 14(17), 3578; https://doi.org/10.3390/nu14173578 - 30 Aug 2022

Cited by 11 | Viewed by 2864

Abstract

In the last decade, data has suggested that dietary advanced glycation end products (AGEs) play an important role in both reproductive and metabolic dysfunctions associated with polycystic ovary syndrome (PCOS). AGEs are highly reactive molecules that are formed by the non-enzymatic glycation process [...] Read more.

In the last decade, data has suggested that dietary advanced glycation end products (AGEs) play an important role in both reproductive and metabolic dysfunctions associated with polycystic ovary syndrome (PCOS). AGEs are highly reactive molecules that are formed by the non-enzymatic glycation process between reducing sugars and proteins, lipids, or nucleic acids. They can be formed endogenously under normal metabolic conditions or under abnormal situations such as diabetes, renal disease, and other inflammatory disorders. Bodily AGEs can also accumulate from exogenous dietary sources particularly when ingested food is cooked and processed under high-temperature conditions, such as frying, baking, or grilling. Women with PCOS have elevated levels of serum AGEs that are associated with insulin resistance and obesity and that leads to a high deposition of AGEs in the ovarian tissue causing anovulation and hyperandrogenism. This review will describe new data relevant to the role of AGEs in several key elements of PCOS phenotype and pathophysiology. Those elements include ovarian dysfunction, hyperandrogenemia, insulin resistance, and obesity. The literature findings to date suggest that targeting AGEs and their cellular actions could represent a novel approach to treating PCOS symptoms. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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13 pages, 325 KiB

Open AccessEditor’s ChoiceReview

Advanced Glycation End Products and Their Effect on Vascular Complications in Type 2 Diabetes Mellitus

by Jeongmin Lee, Jae-Seung Yun and Seung-Hyun Ko

Nutrients 2022, 14(15), 3086; https://doi.org/10.3390/nu14153086 - 27 Jul 2022

Cited by 45 | Viewed by 4950

Abstract

Diabetes is well established as a chronic disease with a high health burden due to mortality or morbidity from the final outcomes of vascular complications. An increased duration of hyperglycemia is associated with abnormal metabolism. Advanced glycation end products (AGEs) are nonenzymatic glycated [...] Read more.

Diabetes is well established as a chronic disease with a high health burden due to mortality or morbidity from the final outcomes of vascular complications. An increased duration of hyperglycemia is associated with abnormal metabolism. Advanced glycation end products (AGEs) are nonenzymatic glycated forms of free amino acids that lead to abnormal crosslinking of extra-cellular and intracellular proteins by disrupting the normal structure. Furthermore, the interaction of AGEs and their receptors induces several pathways by promoting oxidative stress and inflammation. In this review, we discuss the role of AGEs in diabetic vascular complications, especially type 2 DM, based on recent clinical studies. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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22 pages, 890 KiB

Open AccessEditor’s ChoiceReview

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders

by Nathan M. D’Cunha, Domenico Sergi, Melissa M. Lane, Nenad Naumovski, Elizabeth Gamage, Anushri Rajendran, Matina Kouvari, Sarah Gauci, Thusharika Dissanayka, Wolfgang Marx and Nikolaj Travica

Nutrients 2022, 14(12), 2421; https://doi.org/10.3390/nu14122421 - 10 Jun 2022

Cited by 29 | Viewed by 11202

Abstract

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of [...] Read more.

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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12 pages, 11368 KiB

Open AccessReview

Impact of Dietary Advanced Glycation End Products on Female Reproduction: Review of Potential Mechanistic Pathways

by Marco Mouanness and Zaher Merhi

Nutrients 2022, 14(5), 966; https://doi.org/10.3390/nu14050966 - 24 Feb 2022

Cited by 12 | Viewed by 3949

Abstract

Advanced glycation end products (AGEs), a heterogenous group of products formed by the reaction between protein and reducing sugars, can form endogenously due to non-enzymatic reactions or by exogenous sources such as diet where considerable increase in AGEs is observed due to the [...] Read more.

Advanced glycation end products (AGEs), a heterogenous group of products formed by the reaction between protein and reducing sugars, can form endogenously due to non-enzymatic reactions or by exogenous sources such as diet where considerable increase in AGEs is observed due to the modification of food mainly by thermal processing. Recent studies have suggested that AGEs could impact, via inducing inflammation and oxidative stress, the reproductive health and fertility in both males and females. This review presents a summary of recently published data pertaining to the pathogenesis of dietary AGEs and their receptors as well as their potential impact on female reproductive health. More specifically, it will present data pertaining to dietary AGEs’ involvement in the mechanistic pathogenesis of polycystic ovary syndrome, ovarian dysfunction, as well as the AGEs’ effect perinatally on the female offspring reproduction. Understanding the mechanistic impact of dietary AGEs on female reproduction can help contribute to the development of targeted pharmacological therapies that will help curb rising female infertility. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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36 pages, 1155 KiB

Open AccessReview

In Vitro Methodologies to Study the Role of Advanced Glycation End Products (AGEs) in Neurodegeneration

by Marialena Chrysanthou, Ignacio Miro Estruch, Ivonne M. C. M. Rietjens, Harry J. Wichers and Tamara Hoppenbrouwers

Nutrients 2022, 14(2), 363; https://doi.org/10.3390/nu14020363 - 15 Jan 2022

Cited by 18 | Viewed by 5398

Abstract

Advanced glycation end products (AGEs) can be present in food or be endogenously produced in biological systems. Their formation has been associated with chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. The implication of AGEs in [...] Read more.

Advanced glycation end products (AGEs) can be present in food or be endogenously produced in biological systems. Their formation has been associated with chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. The implication of AGEs in neurodegeneration is related to their ability to bind to AGE-specific receptors and the ability of their precursors to induce the so-called “dicarbonyl stress”, resulting in cross-linking and protein damage. However, the mode of action underlying their role in neurodegeneration remains unclear. While some research has been carried out in observational clinical studies, further in vitro studies may help elucidate these underlying modes of action. This review presents and discusses in vitro methodologies used in research on the potential role of AGEs in neuroinflammation and neurodegeneration. The overview reveals the main concepts linking AGEs to neurodegeneration, the current findings, and the available and advisable in vitro models to study their role. Moreover, the major questions regarding the role of AGEs in neurodegenerative diseases and the challenges and discrepancies in the research field are discussed. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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Jump to: Research, Review

12 pages, 1837 KiB

Open AccessSystematic Review

Advanced Glycation End-Products in Common Non-Infectious Liver Diseases: Systematic Review and Meta-Analysis

by Kamil Litwinowicz, Ewa Waszczuk and Andrzej Gamian

Nutrients 2021, 13(10), 3370; https://doi.org/10.3390/nu13103370 - 25 Sep 2021

Cited by 10 | Viewed by 3362

Abstract

Background: Excessive intake of fructose, glucose and alcohol is associated with the development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). At the same time, these dietetic factors create an environment favorable for the generation of advanced glycation end-products. For [...] Read more.

Background: Excessive intake of fructose, glucose and alcohol is associated with the development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). At the same time, these dietetic factors create an environment favorable for the generation of advanced glycation end-products. For this reason, advanced glycation end-products (AGEs) are hypothesized to play role in the development of NAFLD and ALD. In this systematic review and meta-analysis, we explore the relationship between NAFLD and ALD with AGE levels, including their diagnostic accuracy. Methods: The systematic review and meta-analysis has been pre-registered with PROSPERO (CRD42021240954) and was performed in accordance with the PRISMA guidelines. Meta-analyses were performed using the meta R package. Results: We have obtained 11 studies meeting our inclusion criteria, reporting data on 1844 participants (909 with NAFLD, 169 with ALD and 766 healthy controls). NAFLD was associated with significantly higher AGE fluorescence and serum N-(carboxyethyl)lysine (CEL) levels. Patients with alcoholic cirrhosis had significantly higher levels of N-(carboxymethyl)lysine (CML). Only individual studies examined AGEs in the context of their diagnostic accuracy. AGE fluorescence distinguished low and moderate steatosis with an AUC of 0.76. The ratio of CML, CEL and pentosidine to a soluble variant of the AGE receptor differentiated patients with NAFLD from healthy controls with high AUC (0.83–0.85). Glyceraldehyde-derived AGE separated non-alcoholic fatty liver (NAFL) from non-alcoholic steatohepatitis (NASH) with acceptable performance (AUC 0.78). Conclusions: In conclusion, NAFLD and ALD are associated with significantly higher levels of several AGEs. More research is needed to examine the diagnostic accuracy of AGEs, however individual studies show that AGEs perform well in distinguishing NAFL from NASH. Full article

(This article belongs to the Special Issue Advanced Glycation End Products (AGEs): Link between Modern Health and Disease)

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