Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects

Yamagishi, Sho‐ichi; Adachi, Hisashi; Nakamura, Kazuo; Matsui, Takanori; Jinnouchi, Yuko; Takenaka, Katsuto; Takeuchi, Masayoshi; Enomoto, Masaru; Furuki, Kumiko; Hino, Asuka; Shigeto, Yoshiyuki; Imaizumi, Tsutomu

doi:10.1016/j.metabol.2006.05.007

Cited by 137 publications

(130 citation statements)

References 30 publications

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“…There are other studies depicting a link between BMI, waist circumference and sRAGE, but those are cross-sectional studies that are in contrast to our study. 18,19 Interestingly, in the large CARDS trial, 20 patients with lower BMI levels had higher levels of sRAGE, which is in line with our longitudinal data demonstrating that sRAGE levels increase after weight loss. sRAGE acts as a decoy to protect one from AGE-mediated damage.…”

Section: Discussionsupporting

confidence: 85%

“…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%

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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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Section: Discussionsupporting

confidence: 85%

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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“…Enhanced production of reactive oxygen species, probably due to vascular ischemia and reperfusion injury following Raynaud's phenomenon [53,54], may increase HMGB-1, leading to production of sRAGE as a counter-system against HMGB-1/RAGE-induced inflammatory responses [23,38]. Consistent with this, in this study, HMGB-1 and sRAGE levels were associated with vascular damage, such as renal vascular damage, nailfold bleeding, and pitting scar/ulcer.…”

Section: Serum Levels Of Hmgb-1 and Srage In Sscsupporting

confidence: 82%

“…Furthermore, the finding of Yamagishi et al suggest that circulating sRAGE levels may reflect tissue RAGE expression and may be elevated in parallel with RAGE ligands, such as HMGB-1, as a counter-system against RAGE ligand-elicited tissue damage [23,38]. Actually, in our present study,…”

Section: Discussionsupporting

confidence: 43%

Clinical Significance of Serum HMGB-1 and sRAGE Levels in Systemic Sclerosis: Association with Disease Severity

et al. 2008

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The high mobility group box 1 protein (HMGB-1)/adcanced glycation end products (RAGE) system is recently shown to play an important part in immune/inflammatory disorders. However, the association of this system in systemic sclerosis (SSc) remains unknown. To determine clinical association of serum levels of HMGB-1 and soluble RAGE (sRAGE) in patients with SSc, sera from 70 patients with SSc and 25 healthy controls were examined by enzyme-linked immunosorbent assay. Sera from Tight-skin mice and bleomycin-induced scleroderma mice, animal models for SSc, were also examined. Skin HMGB-1 and RAGE expression was assessed by immunohistochemistry. Serum HMGB-1 and sRAGE levels in SSc were higher than those in controls. Similarly, HMGB-1 and sRAGE levels in animal SSc models were higher than those in control mice. SSc patients with elevated HMGB-1 and sRAGE levels had more frequent involvement of several organs and immunological abnormalities compared to those with normal levels. Furthermore, HMGB-1 and sRAGE levels correlated positively with modified Rodnan total skin thickness score and negatively with pulmonary function test. HMGB-1 and sRAGE expression in the sclerotic skin was more intense than normal skin. These results suggest that elevated serum HMGB-1 and sRAGE levels are associated with the disease severity and

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“…The majorities of these correlations remained significant even when the non-diabetic or type 2 diabetic subpopulation was extracted for analyses. An inverse correaltion between esRAGE (or sRAGE) and body mass index was also found for control subjects 115 , those with type 1 diabetes 116 , and those with ESRD 114. Patients with hypertension have been found to have lower plasma sRAGE or esRAGE levels 15,117 .…”

Section: Circulating Srage Esrage and Metabolic Syndromementioning

confidence: 71%

AGE/RAGE as a Mediator of Insulin Resistance or Metabolic Syndrome: Another Aspect of Metabolic Memory?

Koyama¹,

Yamamoto²

2012

Biomedical Science, Engineering and Technology

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Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects

Cited by 137 publications

References 30 publications

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

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

Clinical Significance of Serum HMGB-1 and sRAGE Levels in Systemic Sclerosis: Association with Disease Severity

AGE/RAGE as a Mediator of Insulin Resistance or Metabolic Syndrome: Another Aspect of Metabolic Memory?

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