Advanced glycation end products as one of the “trigger” factors in the development of type 2 diabetes in individuals with obesity
https://doi.org/10.14341/omet13059
Abstract
Consuming high-calorie and thermally processed foods leads to increased body weight and increased levels of advanced glycation end products (AGE) in the human body. AGE has been shown to contribute to dietary oxidative stress and processes that play a major role in the development of type 2 diabetes mellitus (T2DM). Data obtained from cellular and mouse models indicate that the interaction of AGEs with their receptor, RAGE (receptor for advanced glycation end products), promotes the development of inflammation in adipose tissue (AT) through the activation of pro-inflammatory signaling cascades. In addition, there is new evidence, which shows influence of RAGE on the transformation of AT macrophages into the provoking M1 phenotype, which also promotes the degree of inflammation in AT. Inflammation in AT leads to the development of insulin resistance and, accordingly, T2DM. At the same time, there are also RAGE isoforms that can prevent the start of the inflammatory process. The review is devoted to modern views on the role of AGE-RAGE systems in the development of carbohydrate metabolism disorders in obese people.
About the Authors
A. O. Tomilova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Alina O. Tomilova (Gavrilova) - MD, PhD student.
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
E. A. Shestakova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Ekaterina A. Shestakova - MD, PhD, chief research associate.
Moscow
Competing Interests:
None
M. D. Samsonova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Margarita D. Samsonova - MD, clinical resident.
Moscow
Competing Interests:
None
M. V. Shestakova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Marina V. Shestakova - MD, PhD, Professor.
Moscow
Competing Interests:
None
References
1. Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6-10. doi: https://doi.org/10.1016/j.metabol.2018.09.005
2. La Sala L, Pontiroli AE. Prevention of Diabetes and Cardiovascular Disease in Obesity. Int J Mol Sci. 2020;21(21):8178. doi: https://doi.org/10.3390/ijms21218178
3. Feng Z, Zhu L, Wu J. RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage. Adipocyte. 2020;9(1):563-566. doi: https://doi.org/10.1080/21623945.2020.1817278
4. Ruiz HH, Nguyen A, Wang C, et al. AGE/RAGE/DIAPH1 axis is associated with immunometabolic markers and risk of insulin resistance in subcutaneous but not omental adipose tissue in human obesity. Int J Obes. 2021;45(9):2083-2094. doi: https://doi.org/10.1038/s41366-021-00878-3
5. Wautier MP, Guillausseau PJ, Wautier JL. Activation of the receptor for advanced glycation end products and consequences on health. Diabetes Metab Syndr Clin Res Rev. 2017. doi: https://doi.org/10.1016/j.dsx.2016.09.009
6. Vlassara H, Striker GE. AGE restriction in diabetes mellitus: a paradigm shift. Nat Rev Endocrinol. 2011;7(9):526-539. doi: https://doi.org/10.1038/nrendo.2011.74
7. de Courten B, de Courten MP, Soldatos G, et al. Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial. Am J Clin Nutr. 2016;103(6):1426-1433. doi: https://doi.org/10.3945/ajcn.115.125427
8. Gaens KHJ, Goossens GH, Niessen PM, et al. N ε -(Carboxymethyl)lysine-Receptor for Advanced Glycation End Product Axis Is a Key Modulator of Obesity-Induced Dysregulation of Adipokine Expression and Insulin Resistance. Arterioscler Thromb Vasc Biol. 2014;34(6):1199-1208. doi: https://doi.org/10.1161/ATVBAHA.113.302281
9. Snelson M, Coughlan M. Dietary Advanced Glycation End Products: Digestion, Metabolism and Modulation of Gut Microbial Ecology. Nutrients. 2019;11(2):215. doi: https://doi.org/10.3390/nu11020215
10. Ivannikova EV, Smirnova OM. The role of glycation end products and their receptors in the development of diabetes complications // Effective pharmacotherapy. 2019;15(5):20-27. (In Russ.)
11. Jangde N, Ray R, Rai V. RAGE and its ligands: from pathogenesis to therapeutics. Crit Rev Biochem Mol Biol. 2020;55(6):555-575. doi: https://doi.org/10.1080/10409238.2020.1819194
12. Feng Z, Du Z, Shu X, et al. Role of RAGE in obesity-induced adipose tissue inflammation and insulin resistance. Cell Death Discov. 2021;7(1):305. doi: https://doi.org/10.1038/s41420-021-00711-w
13. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced Glycation End Products. Circulation. 2006;114(6):597-605. doi: https://doi.org/10.1161/CIRCULATIONAHA.106.621854
14. Schmidt AM, Yan S Du, Yan SF, Stern DM. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest. 2001;108(7):949-955. doi: https://doi.org/10.1172/JCI200114002
15. Rogge MM. The role of impaired mitochondrial lipid oxidation in obesity. Biol Res Nurs. 2009. doi: https://doi.org/10.1177/1099800408329408
16. Kong Y, Liu C, Zhou Y, et al. Progress of RAGE Molecular Imaging in Alzheimer’s Disease. Front Aging Neurosci. 2020;12. doi: https://doi.org/10.3389/fnagi.2020.00227
17. Prasad K, Khan AS, Bhanumathy KK. Does AGE–RAGE Stress Play a Role in the Development of Coronary Artery Disease in Obesity? Int J Angiol. 2022;31(01):001-009. doi: https://doi.org/10.1055/s-0042-1742587
18. Reddy VP, Aryal P, Darkwah EK. Advanced Glycation End Products in Health and Disease. Microorganisms. 2022;10(9):1848. doi: https://doi.org/10.3390/microorganisms10091848
19. Gavrilova AO, Severina AS, Shamhalova MS, et al. The role of advanced glycation end products in patogenesis of diabetic nephropathy. Diabetes Mellit. 2022;24(5):461–469 (In Russ.) doi: https://doi.org/10.14341/DM12784
20. Kalandiya MM, Tokmakova AYu, Galstyan GR. The role of glycation end products in the development and progression of diabetic neuroarthropathy. Probl. Endocrinol. 2021; 67(3):4–9 (In Russ.) doi: https://doi.org/10.14341/probl12778
21. Miranda ER, Somal VS, Mey JT, et al. Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose-tolerant individuals and are associated with the development of type 2 diabetes. Am J Physiol - Endocrinol Metab. 2017. doi: https://doi.org/10.1152/ajpendo.00146.2017
22. Tavares JF, Ribeiro PVM, Coelho OGL, Silva LE da, Alfenas RCG. Can advanced glycation end‐products and their receptors be affected by weight loss? A systematic review. Obes Rev. 2020;21(6). doi: https://doi.org/10.1111/obr.13000
23. Püschel GP, Klauder J, Henkel J. Macrophages, Low-Grade Inflammation, Insulin Resistance and Hyperinsulinemia: A Mutual Ambiguous Relationship in the Development of Metabolic Diseases. J Clin Med. 2022. doi: https://doi.org/10.3390/jcm11154358
24. Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003. doi: https://doi.org/10.1172/JCI200319451
25. Byun K, Yoo Y, Son M, et al. Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases. Pharmacol Ther. 2017;177:44-55. doi: https://doi.org/10.1016/j.pharmthera.2017.02.030
26. Xu Y, Toure F, Qu W, et al. Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling and Up-regulation of Egr-1 in Hypoxic Macrophages. J Biol Chem. 2010;285(30):23233-23240. doi: https://doi.org/10.1074/jbc.M110.117457
27. Schmidt AM. RAGE and Implications for the Pathogenesis and Treatment of Cardiometabolic Disorders – Spotlight on the Macrophage. Arterioscler. Thromb. Vasc. Biol. 2017;37(4):613–621 doi: https://doi.org/10.1161/ATVBAHA.117.307263
28. Monden M, Koyama H, Otsuka Y, et al. Receptor for Advanced Glycation End Products Regulates Adipocyte Hypertrophy and Insulin Sensitivity in Mice. Diabetes. 2013;62(2):478-489. doi: https://doi.org/10.2337/db11-1116
29. Sayej WN, Knight PR, Guo WA, et al. Advanced Glycation End Products Induce Obesity and Hepatosteatosis in CD-1 Wild-Type Mice. Biomed Res Int. 2016. doi: https://doi.org/10.1155/2016/7867852
30. Song F, Hurtado del Pozo C, Rosario R, et al. RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice. Diabetes. 2014;63(6):1948-1965. doi: https://doi.org/10.2337/db13-1636
31. Ueno H, Koyama H, Shoji T, et al. Receptor for advanced glycation end-products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in apoE-deficient mouse. Atherosclerosis. 2010. doi: https://doi.org/10.1016/j.atherosclerosis.2010.04.006
32. Hurtado del Pozo C, Ruiz HH, Arivazhagan L, et al. A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis. Cell Rep. 2019;28(3):773-791.e7. doi: https://doi.org/10.1016/j.celrep.2019.06.06133.
33. Villarreal-Calderon JR, Cuellar-Tamez R, Castillo EC, Luna-Ceron E, García-Rivas G, Elizondo-Montemayor L. Metabolic shift precedes the resolution of inflammation in a cohort of patients undergoing bariatric and metabolic surgery. Sci Rep. 2021;11(1):12127. doi: https://doi.org/10.1038/s41598-021-91393-y
34. Kamei N, Tobe K, Suzuki R, et al. Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance. J Biol Chem. 2006;281(36):26602-26614. doi: https://doi.org/10.1074/jbc.M601284200
35. Turki Jalil A, Alameri AA, Iqbal Doewes R, et al. Circulating and dietary advanced glycation end products and obesity in an adult population: A paradox of their detrimental effects in obesity. Front Endocrinol (Lausanne). 2022;13. doi: https://doi.org/10.3389/fendo.2022.966590
36. Ruiz HH, Ramasamy R, Schmidt AM. Advanced Glycation End Products: Building on the Concept of the “Common Soil” in Metabolic Disease. Endocrinology. 2020;161(1). doi: https://doi.org/10.1210/endocr/bqz006
37. Šebeková K, Krivošíková Z, Gajdoš M. Total plasma Nε-(carboxymethyl)lysine and sRAGE levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects. Clin Chem Lab Med. 2014;52(1). doi: https://doi.org/10.1515/cclm-2012-0879
38. Uribarri J, Cai W, Woodward M, et al. Elevated Serum Advanced Glycation Endproducts in Obese Indicate Risk for the Metabolic Syndrome: A Link Between Healthy and Unhealthy Obesity? J Clin Endocrinol Metab. 2015;100(5):1957-1966. doi: https://doi.org/10.1210/jc.2014-3925
39. Dozio E, Briganti S, Delnevo A, et al. Relationship between soluble receptor for advanced glycation end products (sRAGE), body composition and fat distribution in healthy women. Eur J Nutr. 2017. doi: https://doi.org/10.1007/s00394-016-1291-0
40. Koborová I, Gurecká R, Csongová M, et al. Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and the activity of semicarbazide-sensitive amine oxidase. Croat Med J. 2017. doi: https://doi.org/10.3325/cmj.2017.58.106
41. Norata GD, Garlaschelli K, Grigore L, et al. Circulating soluble receptor for advanced glycation end products is inversely associated with body mass index and waist/hip ratio in the general population. Nutr Metab Cardiovasc Dis. 2009;19(2):129-134. doi: https://doi.org/10.1016/j.numecd.2008.03.004
42. Guclu M, Ali A, Eroglu DU, Büyükuysal SO, Cander S, Ocak N. Serum Levels of sRAGE Are Associated with Body Measurements, but Not Glycemic Parameters in Patients with Prediabetes. Metab Syndr Relat Disord. 2016;14(1):33-39. doi: https://doi.org/10.1089/met.2015.0078
43. Davis KE, Prasad C, Vijayagopal P, Juma S, Imrhan V. Serum soluble receptor for advanced glycation end products correlates inversely with measures of adiposity in young adults. Nutr Res. 2014;34(6):478-485. doi: https://doi.org/10.1016/j.nutres.2014.04.012
44. Uribarri J, Woodruff S, Goodman S, et al. Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet. J Am Diet Assoc. 2010. doi: https://doi.org/10.1016/j.jada.2010.03.018
45. Gugliucci A, Kotani K, Taing J, et al. Short-Term Low Calorie Diet Intervention Reduces Serum Advanced Glycation End Products in Healthy Overweight or Obese Adults. Ann Nutr Metab. 2009;54(3):197-201. doi: https://doi.org/10.1159/000217817
46. Miranda ER, Fuller KNZ, Perkins RK, et al. Endogenous secretory RAGE increases with improvements in body composition and is associated with markers of adipocyte health. Nutr Metab Cardiovasc Dis. 2018;28(11):1155-1165. doi: https://doi.org/10.1016/j.numecd.2018.07.009
47. Brix JM, Höllerl F, Kopp H-P, Schernthaner GH, Schernthaner G. The soluble form of the receptor of advanced glycation endproducts increases after bariatric surgery in morbid obesity. Int J Obes. 2012;36(11):1412-1417. doi: https://doi.org/10.1038/ijo.2012.107
48. Horwitz D, Saunders JK, Ude-Welcome A, et al. Three-year follow-up comparing metabolic surgery versus medical weight management in patients with type 2 diabetes and BMI 30–35. The role of sRAGE biomarker as predictor of satisfactory outcomes. Surg Obes Relat Dis. 2016;12(7):1337-1341. doi: https://doi.org/10.1016/j.soard.2016.01.016
Supplementary files
|
|
1. Figure 1. Structure of the receptor for advanced glycation end products (RAGE) and its isoform sRAGE | |
| Subject | ||
| Type | Исследовательские инструменты | |
View
(109KB)
|
Indexing metadata ▾ | |
|
|
2. Figure 2. Visual representation of the results of studies investigating the role of RAGE in adipose tissue in mouse models | |
| Subject | ||
| Type | Исследовательские инструменты | |
View
(263KB)
|
Indexing metadata ▾ | |
|
|
3. Figure 3. Schematic representation of changes in the AGE-RAGE system during the development of obesity and diabetes | |
| Subject | ||
| Type | Исследовательские инструменты | |
View
(259KB)
|
Indexing metadata ▾ | |
Review
For citations:
Tomilova A.O., Shestakova E.A., Samsonova M.D., Shestakova M.V. Advanced glycation end products as one of the “trigger” factors in the development of type 2 diabetes in individuals with obesity. Obesity and metabolism. 2024;21(3):302-308. (In Russ.) https://doi.org/10.14341/omet13059
Views:
1555
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
