Circulating soluble receptor for advanced glycation end products is inversely associated with body mass index and waist/hip ratio in the general population

Norata, Giuseppe Danilo; Garlaschelli, K.; Grigore, Liliana; Tibolla, G.; Raselli, Sara; Redaelli, L.; Buccianti, G.; Catapano, Alberico L.

doi:10.1016/j.numecd.2008.03.004

Cited by 98 publications

(91 citation statements)

References 18 publications

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“…Similar to the study by Sebekova et al [10], we found an inverse relationship between log 10 CML and the multiple markers of adiposity and adiposity-related comorbidity risk factors (IL-6, and LDL). However, Sebekova did not find the inverse association between sRAGE and indices of body fatness and insulin release seen in our study and in many adult studies [26]. In contrast to Sebekova et al [10], a recent study of 130 prepubertal children (younger than those examined in the present study) by Chiavaroli et al [11] reported significant negative correlations of both sRAGE and esRAGE with adiposity and insulin resistance and also noted independently lower concentrations of sRAGE and esRAGE in children who were at increased risk of adiposity-related comorbidities by virtue of being small or large for gestational age.…”

Section: Discussioncontrasting

confidence: 91%

Plasma Advanced Glycation End Products (AGEs), Receptors for AGEs and Their Correlation with Inflammatory Markers in Middle School-Age Children

Accacha

Rosenfeld

Jacobson³

et al. 2013

Horm Res Paediatr

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Aim: Advanced glycation end products (AGEs) and/or their receptors (RAGE) are significantly positively correlated with adiposity, inflammation, dyslipidemia, and insulin resistance in adults. However, the relationships between AGEs, RAGE, and adiposity-related comorbidites in children have not been well studied. Methods: In a cross-sectional study of 88 children (age 11-15 years) from the New York area enrolled in the Reduce Obesity and Diabetes (ROAD) study, we examined the correlation of the AGE N^ε-(carboxymethyl)lysine (CML), soluble RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) with adiposity, inflammatory markers [interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-α], adiponectin, lipids, insulin sensitivity, and insulin secretory capacity. Results: Pediatric CML levels were ∼20% below average adult levels. CML was significantly (p < 0.05) positively correlated with age and insulin sensitivity and negatively with adiposity, dyslipidemia and IL-6. sRAGE correlated positively with esRAGE and negatively with adiposity and IL-6. Both sRAGE and esRAGE correlated negatively with insulin secretory capacity. Conclusion: Our findings suggest that unlike adults, CML is negatively associated with adiposity and adiposity-related comorbidity risk in children. As in adults, sRAGE and esRAGE were, to varying degrees, negatively correlated with body fatness and risk factors for adiposity-related comorbidities.

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Section: Discussioncontrasting

confidence: 91%

Plasma Advanced Glycation End Products (AGEs), Receptors for AGEs and Their Correlation with Inflammatory Markers in Middle School-Age Children

Accacha

Rosenfeld

Jacobson³

et al. 2013

Horm Res Paediatr

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“…sRAGE is a C-truncated variant of RAGE, a 50-kDa protein, and is mainly produced by splicing or cleavage from cell surface through metalloproteinases in endothelial cells. 27 Norata et al 17 showed an association between sRAGE levels and BMI as well as waist/hip ratio in a general population. In this study, only patients without CV diseases and diabetes were included and the authors could demonstrate an inverse correlation between sRAGE levels and factors of the metabolic syndrome such as BMI, waist/hip ratio and fasting glucose in 176 subjects.…”

Section: Discussionmentioning

confidence: 98%

“…16 The existing data about sRAGE and cardiovascular (CV) risk are rather controversial, but there is one finding that is consistent in all studies-an inverse correlation between sRAGE levels with BMI. [17][18][19][20][21] However, up to now nearly all studies about sRAGE were done in a crosssectional setting. [4][5][6]13 Morbid obesity (MO) is a pandemic, worldwide disease with still increasing numbers, 22 and bariatric surgery is one of the most frequent surgeries in the Western World.…”

Section: Introductionmentioning

confidence: 99%

The soluble form of the receptor of advanced glycation endproducts increases after bariatric surgery in morbid obesity

Höllerl

et al. 2012

Int J Obes

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OBJECTIVE:The increased cardiovascular (CV) disease risk in patients with morbid obesity (MO) cannot be fully explained by traditional CV risk factors. Activation of the receptor of Advanced Glycation Endproducts (RAGE) leads to inflammation via the NF kb (nuclear factor kb) pathway. The soluble form of RAGE (sRAGE), which is present in plasma, can bind to ligands of RAGE and avoids interaction of RAGE with proinflammatory ligands. We investigated sRAGE levels in patients with MO and compared them with healthy lean controls (CO), before and after bariatric surgery. DESIGN: We conducted a cross-sectional study and a 24-month longitudinal study. SUBJECTS: We included 85 patients (mean age: 41±12 years; mean body mass index (BMI): 45.4±7.9 kg m À 2 ) with MO in comparison with 40 CO (mean age: 42 ± 13 years; mean BMI: 26.0 ± 5.5 kg m À 2 ). All patients were investigated before and 2 years after bariatric surgery. Apart from weight and CV risk markers (blood pressure, lipids), a glucose tolerance test (75 g), renal and inflammation parameters were assessed. sRAGE levels were assessed by a commercial ELISA. To investigate the associations of the observed reductions of values, delta (D) of parameters were calculated. RESULTS: Patients with MO had significant lower sRAGE levels than CO: 1010 ± 514 vs 1501 ± 674 pg ml À 1 ; Po0.001. In the longitudinal study, sRAGE levels increased significantly after bariatric surgery from 1010±514 to 1261±710 pg ml À 1 ; P ¼ 0.008. In the correlation analysis, DsRAGE levels were associated with D1-h and D2-h postprandial glucose, Dfasting insulin, D2-h postprandial insulin, DHOMA (homeostatic model assessment)-insulin resistance (DHOMA-IR), Dg-glutamyl transferase and Dtriglycerides. In a multivariate model, D1-h and D2-h postprandial glucose, D2-h postprandial insulin and DHOMA-IR predicted DsRAGE. CONCLUSION: Patients with MO have significantly lower sRAGE levels compared with non-obese CO, but sRAGE levels increase significantly after weight loss induced by bariatric surgery. As high sRAGE levels inhibit the activation of inflammatory pathways, our results might help understand the beneficial effects of bariatric surgery regarding CV morbidity and mortality. Keywords: morbid obesity; sRAGE; insulin resistance; prospective INTRODUCTION Hyperglycemia leads to non-enzymatic glycation of intracellular and extracellular protein by forming advanced glycation endproducts (AGEs). 1 The RAGE (receptor of AGEs), a multi-ligand member of the immunoglobulin superfamily of transmembrane cell surface molecules, is a specific membrane-bound receptor for AGEs, 2 and activation of the RAGE by AGEs has a major role in the pathogenesis of diabetic vascular complications by way of activation of the NF kb (nuclear factor kb) pathway. 3 sRAGE is the soluble receptor of RAGE existing in the circulation. sRAGE levels have been found to be associated with chronic inflammatory diseases, including atherosclerosis and diabetes. 4-6 sRAGE acts as a decoy to prevent an interaction between AGE and RAGE and ther...

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“…The soluble form of RAGE (sRAGE) appears to act as an AGE quencher and may have a protective effect [17] . Interestingly, a recent report showed that sRAGE is negatively and significantly correlated with BMI and waist/hip circumference ratio [18] . Hence, the first mechanism for serum AGE reduction in our cohort may be an increase in sRAGE produced by lowering BMI, which in turn acts by reducing the circulating load of AGEs.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Low Calorie Diet Intervention Reduces Serum Advanced Glycation End Products in Healthy Overweight or Obese Adults

et al. 2009

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Background: Obesity is a metabolic and cardiovascular risk factor. A low calorie diet (LCD) is one of the treatment modalities for weight loss. Serum advanced glycation end products (AGEs) are linked to increased atherogenicity and inflammation in diseases such as diabetes and renal failure. Obesity has an inflammatory component, but interestingly there are no studies on serum AGE levels in obesity or on the effects of LCD as a therapeutic measure on these markers of glycation. Aim: We hypothesized that weight loss by caloric restriction has a beneficial effect on serum AGE levels. We investigated the prospective effects of a sole LCD intervention for weight loss on serum AGEs in a cohort of overweight and non-morbidly obese but otherwise healthy subjects. Methods: A total of 37 Japanese subjects (30 females, 7 males, mean age 48.2 ± 9.3 years) with a mean BMI of 28.3 ± 3.2 participated in this study. During the intervention period of 2 months, they were placed on an LCD (Diet’s™; 5,023 kJ/day) with meal replacement every dinner. The following data were evaluated pre- and post-intervention: AGEs, BMI, waist circumference, blood pressure, serum glucose, cholesterol, triglycerides, HDL- and LDL- cholesterol. Results and Discussion: After the intervention, BMI levels were clearly reduced by 6.3% (p < 0.001), waist circumference by 5.7% (p < 0.002) and triglycerides by 11.9 % (p < 0.002). At baseline, AGEs levels were 63 ± 11 AU for obese subjects and 63 ± 14 for control subjects (not significant). After intervention, AGEs were reduced by 7.21% (range 0–35%, p < 0.001). The percent change in AGEs was significantly and positively correlated with that of triglycerides (r = 0.42, p < 0.009), waist circumference (r = 0.40, p < 0.011), and BMI (r = 0.42, p < 0.007). We show for the first time that serum AGEs can be reduced by an LCD intervention on weight loss, a change that correlates with the reduction in triglycerides. This may plausibly be a reflection of a reduction in glycation/lipoxidation due to the caloric restriction and its metabolic consequences, or it may be due to the decreased intake of food containing glycotoxins, or a combination of both.

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Circulating soluble receptor for advanced glycation end products is inversely associated with body mass index and waist/hip ratio in the general population

Cited by 98 publications

References 18 publications

Plasma Advanced Glycation End Products (AGEs), Receptors for AGEs and Their Correlation with Inflammatory Markers in Middle School-Age Children

Plasma Advanced Glycation End Products (AGEs), Receptors for AGEs and Their Correlation with Inflammatory Markers in Middle School-Age Children

The soluble form of the receptor of advanced glycation endproducts increases after bariatric surgery in morbid obesity

Short-Term Low Calorie Diet Intervention Reduces Serum Advanced Glycation End Products in Healthy Overweight or Obese Adults

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