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Advanced Glycation End Products: A Sweet Flavor That Embitters Cardiovascular Disease.
Pinto, RS, Minanni, CA, de Araújo Lira, AL, Passarelli, M
International journal of molecular sciences. 2022;(5)
Abstract
Epidemiological studies demonstrate the role of early and intensive glycemic control in the prevention of micro and macrovascular disease in both type 1 and type 2 diabetes mellitus (DM). Hyperglycemia elicits several pathways related to the etiopathogenesis of cardiovascular disease (CVD), including the generation of advanced glycation end products (AGEs). In this review, we revisit the role played by AGEs in CVD based in clinical trials and experimental evidence. Mechanistic aspects concerning the recognition of AGEs by the advanced glycosylation end product-specific receptor (AGER) and its counterpart, the dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST) and soluble AGER are discussed. A special focus is offered to the AGE-elicited pathways that promote cholesterol accumulation in the arterial wall by enhanced oxidative stress, inflammation, endoplasmic reticulum stress and impairment in the reverse cholesterol transport (RCT).
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2.
Metabolic transit of dietary advanced glycation end-products - the case of NƐ-carboxymethyllysine.
Tessier, FJ, Boulanger, E, Howsam, M
Glycoconjugate journal. 2021;(3):311-317
Abstract
The Maillard reaction, also called glycation, is one of the major chemical reactions responsible for most yellow-to-brown colors and aromas in cooked foods. This reaction between reducing sugars and amino functions on proteins affects not only the flavor of food, but also leads to the formation of an heterogenous group of structurally-modified amino acids. Some of these, known as "advanced glycation end products" (AGEs), have been found in both foods and human biological fluids, tissues and organs. Except for those that are formed over long periods in vivo at 37 °C, AGEs in the body originate from the digestion and absorption of dietary sources. A high or chronic exposure to dietary AGEs (dAGEs) is suspected as potentially detrimental to human health and studies in the field of food safety have begun to focus their attention on the metabolic transit of dAGEs. This review presents some important findings in this field, with a focus on NƐ-carboxymethyllysine, and presents the evidence for and against an association between intake of dAGEs and their presence in the body. New and promising avenues of research are described, and some future directions outlined.
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3.
Dietary AGEs as Exogenous Boosters of Inflammation.
Garay-Sevilla, ME, Rojas, A, Portero-Otin, M, Uribarri, J
Nutrients. 2021;(8)
Abstract
Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated).
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4.
Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer's Disease.
Aaseth, J, Skalny, AV, Roos, PM, Alexander, J, Aschner, M, Tinkov, AA
International journal of molecular sciences. 2021;(17)
Abstract
The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer's disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.
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5.
The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction.
Sergi, D, Boulestin, H, Campbell, FM, Williams, LM
Molecular nutrition & food research. 2021;(1):e1900934
Abstract
Advanced glycation end products (AGEs) are a heterogeneous group of molecules produced, non-enzymatically, from the interaction between reducing sugars and the free amino groups of proteins, nucleic acids, and lipids. AGEs are formed as a normal consequence of metabolism but can also be absorbed from the diet. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes, and kidneys. Increased levels of AGEs are also detrimental to metabolic health and may contribute to the metabolic abnormalities induced by the Western diet, which is high in processed foods and represents a significant source of AGEs. While increased AGE levels are a consequence of diabetic hyperglycaemia, AGEs themselves activate signaling pathways, which compromise insulin signaling and pancreatic β-cell function, thus, contributing to the development of type 2 diabetes mellitus (T2DM). Furthermore, AGEs may also contribute to the obesogenic effects of the Western diet by promoting hypothalamic inflammation and disrupting the central control of energy balance. Here, the role of dietary AGEs in metabolic dysfunction is reviewed with a focus on the mechanisms underpinning their detrimental role in insulin resistance, pancreatic β-cell dysfunction, hypothalamic control of energy balance, and the pathogenesis of T2DM and obesity.
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6.
The cardiovascular complications of diabetes: a striking link through protein glycation.
Ahmad, MN, Farah, AI, Al-Qirim, TM
Romanian journal of internal medicine = Revue roumaine de medecine interne. 2020;(4):188-198
Abstract
Diabetes mellitus is a predominant cause of mortality and morbidity worldwide. One of its serious health problems is cardiovascular complications. Advanced glycation end products (AGEs) are a group of heterogeneous toxic oxidant compounds that are formed after a non-enzymatic reaction between monosaccharides and free amino groups of proteins, compound lipids, and nucleic acids. AGE interacts with various types of cells through a receptor for AGE (RAGE). The interaction between AGE and RAGE is responsible for a cascade of inflammation, oxidative stress, and disruption of calcium homeostasis in cardiac cells of diabetic patients. There is striking evidence that the AGE/RAGE axis with its consequences on inflammation and oxidative stress plays a major role in the development of cardiovascular complications. Therefore, considering AGE as a therapeutic target with foreseeable results would be a wise direction for future research. Interestingly, several studies on nutraceutical, pharmaceutical, and natural products have begun to reveal promising therapeutic results, and this could lead to better health outcomes for many diabetic patients worldwide. This article discusses the current literature addressing the connection between protein glycation and diabetes cardiovascular complications and suggests future avenues of research.
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7.
Advanced glycation end products in diabetes, cancer and phytochemical therapy.
Dariya, B, Nagaraju, GP
Drug discovery today. 2020;(9):1614-1623
Abstract
The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products (AGEs). These modified AGEs are triggered to bind the receptor for AGE (RAGE), thereby activating its downstream signaling pathways, such as nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)/Akt, ultimately leading to diabetes and cancers. In this review, we focus on the interaction of AGE-RAGE and their associated pathways. We also consider the activity of phytochemicals, such as genistein and curcumin, that trap dicarbonyl compounds including methylglyoxal (MG) and glyoxalase that arise from multiple pathways to block AGE formation and prevent its interaction with RAGE.
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8.
Functional and biological properties of Maillard conjugates and their potential application in medical and food: A review.
Nooshkam, M, Varidi, M, Verma, DK
Food research international (Ottawa, Ont.). 2020;:109003
Abstract
Protein and peptides are usually sensitive to environmental stresses, such as pH changes, high temperature, ionic strength, and digestive enzymes amongst other, which limit their food and medicinal applications. Maillard reaction (also called Maillard conjugation or glycation) occurs naturally without the addition of chemical agents and has been vastly applied to boost protein/peptide/amino acid functionalities and biological properties. Protein/peptide-saccharide conjugates are currently used as emulsifiers, antioxidants, antimicrobials, gelling agents, and anti-browning compounds in food model systems and products. The conjugates also possess the excellent stabilizing ability as a potent delivery system to enhance the stability and bioaccessibility of many bioactive compounds. Carbonyl scavengers such as polyphenols are able to significantly inhibit the formation of advanced glycation end products without a significant effect on early Maillard reaction products (MRPs) and melanoidins, which are currently applied as functional ingredients. This review paper highlights the technological functionality and biological properties of glycoconjugates in food model systems and products. Recent applications of MRPs in medical sciences are also presented.
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9.
Inhibitory effect of phenolic compounds and plant extracts on the formation of advance glycation end products: A comprehensive review.
Khan, M, Liu, H, Wang, J, Sun, B
Food research international (Ottawa, Ont.). 2020;:108933
Abstract
Advance glycation end products (AGEs) are a diverse group of compounds formed through the non-enzymatic maillard reaction of reducing sugars with the free amino groups in proteins, lipids or nucleic acids. Accumulation of AGEs has been suggested to be a pathogenic mechanism of oxidative stress, inflammation and structural tissue damage leading to chronic vascular problems in many ailments including diabetes, atherosclerosis, neuropathy, retinopathy, nephropathy, aging, and chronic renal disease. Treatment with AGEs inhibitors is believed to be a potential strategy for preventing lifestyle-related diseases. To inhibit the AGEs development is supposed to show part in the inhibition of diabetic problems. Study of dietary bioactive combinations with antiglycation properties delivers future views for inhibition or mediation associated to AGEs complications. Many study show the possibility of dietary constituents to stop AGE development. Therefore, search for natural compounds able to prevent glycation and have the potential therapeutic ability to inhibit diabetes and age associated diseases. The purpose of this review is to critically evaluate the existing literature on different phenolics on AGEs inhibition.
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10.
Advanced Glycation End Products: Building on the Concept of the "Common Soil" in Metabolic Disease.
Ruiz, HH, Ramasamy, R, Schmidt, AM
Endocrinology. 2020;(1)
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Abstract
The role of advanced glycation end products (AGEs) in promoting and/or exacerbating metabolic dysregulation is being increasingly recognized. AGEs are formed when reducing sugars nonenzymatically bind to proteins or lipids, a process that is enhanced by hyperglycemic and hyperlipidemic environments characteristic of numerous metabolic disorders including obesity, diabetes, and its complications. In this mini-review, we put forth the notion that AGEs span the spectrum from cause to consequence of insulin resistance and diabetes, and represent a "common soil" underlying the pathophysiology of these metabolic disorders. Collectively, the surveyed literature suggests that AGEs, both those that form endogenously as well as exogenous AGEs derived from environmental factors such as pollution, smoking, and "Western"-style diets, contribute to the pathogenesis of obesity and diabetes. Specifically, AGE accumulation in key metabolically relevant organs induces insulin resistance, inflammation, and oxidative stress, which in turn provide substrates for excess AGE formation, thus creating a feed-forward-fueled pathological loop mediating metabolic dysfunction.