Table 1.
Summary of dAGEs-related animal studies.
| Author | Animal Model | Diet | Results |
|---|---|---|---|
| Thornton et al. 2020 [15] | C57BL/6 J mice | H-AGEs diet: 16.6% fat, 18.8% protein, 64.6% carbohydrate, 3.73 kcal/g, subjected to heating at 125 °C for 30 min | H-AGEs mice showed a lower number of corpora lutea |
| Rajan et al. 2018 [16] | Swiss albino mice | H-AGEs diet (18% of protein, 64% of carbohydrate, 5.2% of fat) subjected to heating (90 °C for 10 min) to generate diet-derived AGEs | Increased body weight, pro-inflammatory cytokines, chemokines, CML, CRP, HbA1c, BUN, creatinine |
| Deng et al. 2020 [17] | apoE−/− mice | High fat diet (42% fat and 0.2% cholesterol) and normal diet (13% fat, no cholesterol) and aminoguanidine | Elevation in the aortic valve transvalvular velocity, alleviation of LDL, TC reduced HFD-induced CML accumulation and RAGE expression in the aortic valve, and restricted EndMT in the aortic valve calcification |
| Mastrocola et al. 2021 [18] | C57BLKS-Db/Db mice | Standard diet and high fat diet (HFD) and pyridoxamine | Accumulation of AGEs in the liver impaired hepatic sphingolipids metabolism and hepatic insulin signaling, prevented by pyridoxamine |
| Verboven et al. 2018 [19] | Sprague–Dawley rats | High-sugar and high-fat diet (Western diet) | Altered glucose tolerance, early signs of cardiac alteration |
| Chen et al. 2019 [20] | Sprague–Dawley | L-AGEs and H-AGEs diets | H-AGEs diet decreases the total number of epididymal sperm and increases the abnormal sperm ratio |
| Mao et al. 2019 [21] | Sprague–Dawley rats | Low-fat control diet and high-fat diet | High fat diet increased cecal contents and decreased proteobacteria |
| Coughlan et al. 2011 [22] | Sprague–Dawley rats | L-AGEs diet and H-AGEs diet | H-AGEs diet increased cellular pathways linked to b-cell damage and b-cell apoptosis and the incidence of autoimmune diabetes in NOD mice |
| Coughlan et al. 2011 [22] | Sprague–Dawley rats | Daily intraperitoneal injections of either AGEs-modified rat serum albumin (AGE-RSA), RSA at 20 mg/kg/day, or saline (sham) | H-AGEs diet increased cellular pathways linked to b-cell damage and b-cell apoptosis and the incidence of autoimmune diabetes in NOD mice |
| Yuan et al. 2017 [23] | Sprague–Dawley rats | Intraperitoneal injection of high-fat/high-sucrose diet and low-dose streptozocin, untreated diabetic and treated with aminoguanidine hydrochloride (100 mg/Kg/day, i.g., for 8 weeks) | AG reduced serum and renal CML deposition, and improved urine protein and uNGAL in type 2 diabetic rats |
| Borg et al. 2018 [24] | NOD8.3 + NOD/ShiLt +NOD8.3C | H-AGEs diet and L-AGEs diet | Exposure to low dietary AGEs from conception to early postnatal life increased islet hormone secretion ex vivo; reduced insulitis; increased the variance of CD4C and CD8C T cells and cDCs in local lymphoid tissues and proportions of pDCs in the spleen; and altered islet expression of the AGEs, CML, and AGE receptors |
| Lee et al. 2019 [25] | Sprague–Dawley rats | Normal diet and regular, low, or high high-fat high-sucrose diet | L-AGEs showed lower fasting glucose, insulin, HOMA-IR, TC, TG, HDLc levels, higher blood urea nitrogen, n-3 PUFAs, decreased proliferation of the mesangial cells, glomerular capillaries, basement membranes around the glomeruli, lower Firmicutes/Bacteroidetes ratio, and increased Allobaculum |
| Maciejczyk et al. 2018 [26] | male Wistar rats | High fat diet (59.8 kcal% fat, 20.1 kcal% protein, and 20.1 kcal% carbs) and normal diet (g 13.5 kcal% fat, 24 kcal% protein, and 62.5 kcal% carbohydrates) | High fat fed rats showed increased body weight, free fatty acids, glucose, insulin, HOMA-IR index, enzymatic antioxidant activity, total antioxidant/oxidant status and oxidative damage products (TAC, TOS, OSI, and FRAP), activity of NOX and XO) in the cerebral cortex and hypothalamus, and enzymatic antioxidants (GPx, CAT, and SOD-1) in the cerebral cortex |
| Qu et al. 2017 [27] | Sprague–Dawley rats | L-AGEs diet or high-AGEs diet | H-AGEs fed rats showed markedly decreased diversity of cecal microbiota, after 18 weeks of feeding, increased proportion of proteobacteria, and decreased proportion of Bacteroidetes; in the short-term feeding period of 6 weeks, significantly higher relative abundance of five genera, including Prevotella, Oscillibacter, Phascolarctobacterium, Akkermansia, and Gastranaerophilales; higher concentration of ammonia in cecal contents and significantly lower concentration of two other genera, Lachnospiraceae and Mucispirillum at 12 and 18 weeks of feeding; decreased acetate and propionate from 6 to 18 weeks; and modestly increased butyric acid and histological score of colonic tissue |
| Illien-Juünger et al. 2018 [28] | C57BL/6J mice | L-AGEs; containing 7.6 μg/mg AGE and H-AGEs: 40.9 μg/m | H-AGEs fed mice showed elevated serum AGEs levels in female mice, sex- and age-dependent effects on vertebral AGEs accumulation and on vertebral bone microstructure, and decreased vertebral mechanical properties |
| Peppa et al. 2003 [29] | Prediabetic NOD mice | H-AGEs diet produced vy exposure to heating (100 °C for 20–60 s and at 125 °C for 20–30 min) and L-AGEs = identical chow mix without heating | L-AGEs fed mice showed a striking reduction in fasting blood glucose, increased plasma insulin levels, decreased affected (20%) pancreatic islets, low levels of IFN-γ and IL-4, high IL-10-to-actin mRNA ratio, and prevention of Type 1 diabetes transmitted to next generations |
| Peppa et al. 2003 [30] | db/db +/+ and db/db −/+ | H-AGEs diet produced by heating (100 °C for 20–60 min and at 125 °C for 20–30 min), L-AGEs identical chow mix without heating | H-AGEs decreased the albumin/creatinine ratio, increased protein-linked tissue deposition of MG- and CML-like AGEs, delayed closure, lead to less re-epithelialization, and delayed wound healing |
| Vlassara et al. 1992 [31] | Lewis rats and New Zealand White rabbits | Tail vein injections with either AGEs-modified or native RSA (100 mg/kg per day) or AGEs-RSA, followed immediately by i.v. injection of aminoguanidine hydrochloride (100 mg/kg per day) | AGEs’ administration resulted in significantly increased vascular permeability, mononuclear cell migratory activity in subendothelial and periarteriolar spaces in various tissues, markedly defective vasodilatory responses to acetylcholine and nitroglycerin, promoted glomerulosclerosis, and normal characteristics in treated with aminoguanidine |
| Cai et al. 2007 [32] | C57BL/6 mice | H-AGEs diet and L-AGEs diet | L-AGEs fed mice showed amelioration of insulin resistance, albuminuria, and glomerulosclerosis, as well as extended lifespan |
| Hofmann et al. 2002 [33] | db/db (+/+) | H-AGEs diet and L-AGEs diet | L-AGEs fed mice showed reduced body weight, improved responses to both glucose and insulin tolerance tests, increased HDL and lowered CML and MG concentrations, and better preservation of the islets |
| Sandu et al. 2005 [34] | C57/BL6 mice | Regular and high-fat diets | H-AGEs fed mice showed higher body weight, fasting glucose, insulin, serum AGEs, altered pancreatic islet structure and function, plasma 8-isoprostanes, and lower adiponectin |
| Cai et al. 2012 [35] | wild-type C57BL6 mice | Nonheated, isocaloric diet, where the content of AGEs was increased by a single synthetic MG-AGE (MG+) | High fat fed mice showed increased adiposity and premature insulin resistance; severe deficiency of AGER1 and SIRT1 in white adipose tissue, skeletal muscle, and liver; impaired 2-deoxy-glucose uptake; marked changes in insulin receptor IRS-1, IRS-2; Akt activation; and a macrophage and adipocyte shift to a pro-oxidant/inflammatory phenotype |
| Cai et al. 2008 [36] | C57BL/6 mice | Caloric restriction (40% reduction in calories), caloric restriction exposed to heating, the same CR diet, in which the content of (by 15 min at 120 °C, and standard formula) | CR-high AGEs fed mice showed high levels of 8-isoprostanes, AGEs, RAGE, p66shc, low AGER1 and GSH/GSSG levels, insulin resistance, marked myocardial and renal fibrosis, and shortened lifespan |
| Kandaraki et al. 2012 [37] | Wistar rats | L-AGEs diet and H-AGEs diet | H-AGEs fed rats showed reduced GLO-I activity, positively correlated with body weight gain and progesterone levels |
| Zheng et al. 2002 [38] | db/db mice | L-AGEs diet and H-AGEs diet | L-AGEs fed mice showed minimal glomerular pathology; modest increase in urinary albumin/creatinine ratio; extended survival; lower serum; and kidney AGEs low levels of renal cortex TGFb-1, laminin B1 mRNA, a1 IV collagen mRNA, and protein |
Abbreviations: L-AGEs diet = low in advanced glycation end products diet; H-AGEs diet = high in advanced glycation end products diet; HFD = high fat diet; CR = caloric reduction; HF = high fat; CML = Nε-carboxymethyllysine; MG = methylglyoxal; AG = aminoguanidine (AGE-inhibitor); CRP = c reactive protein; HbA1c = hemoglobin A1c; BUN = blood urea nitrogen; LDL = low density lipoprotein; TG = triglycerides; RAGE = advanced glycation end products receptor; EndMT = endothelial to mesenchymal transition; HOMA-IR; TC = tissue culture; HDL = high density lipoprotein; n-3 PUFAs = n-3 polyunsaturated fatty acids; TAC = total antioxidant; TOS = total oxidant status; FRAP = ferric reducing ability; NOX = catalytic subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases; GPx = glutathione peroxidase; CAT = catalase; SOD-1 = Cu, Zn-superoxide dismutase-1; IFN-γ = interferon-γ; IL-4 = interleukin-4; IL-10 = interleukin-10; AGER1 = advanced glycation end product receptor-1; SIRT1 = sirtuin-1; receptor IRS-1 = insulin receptor 1; IRS-2 = insulin receptor 2; Akt = serine/threonine kinase 1; GSH = glutathione, GSSG = glutamic acid, cysteine, and glycine glutathione; TGFb-1 = transforming growth factor beta-1.