Fat Mass Is Inversely Associated with Serum Carboxymethyl-Lysine, An Advanced Glycation End Product, in Adults,

Semba, Richard D.; Arab, Lenore; Sun, Kai; Nicklett, Emily J.; Ferrucci, Luigi

doi:10.3945/jn.111.143172

Cited by 63 publications

(60 citation statements)

References 39 publications

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“…We and others have shown that plasma AGEs are related to adiposity [14,[73][74][75]. In the present study, we confirm these findings by showing the negative association between circulating levels of CML and various measures of adiposity.…”

Section: Discussionsupporting

confidence: 81%

“…It has been proposed that the inverse cross-sectional relationship between circulating AGEs and adiposity may be a direct result of AGEs preferentially depositing in the adipose tissue as opposed to the circulation. This could be due to the fact that adipocytes are known to express CD36, a scavenger receptor that binds AGEs and facilitates endocytosis and degradation of AGEs [75].…”

Section: Discussionmentioning

confidence: 99%

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Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Sourris

Lyons

Dougherty

et al. 2014

Clinical Chemistry and Laboratory Medicine

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Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals. Methods: We measured body mass index (BMI), waistto-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carbo xymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC). Results: Plasma CML concentrations were related to diastolic blood pressure (r = −0.51, p < 0.01) independently of age, sex, BMI and WHR (p < 0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r = 0.47, p < 0.01) before and after adjustment for age, sex, BMI and WHR (p < 0.05). Plasma CML concentrations were related to the pulse pressure before (r = 0.42; p < 0.05) and after adjustment for age, sex, BMI and waist (p < 0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p = ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p = ns). Conclusions: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Sourris

Lyons

Dougherty

et al. 2014

Clinical Chemistry and Laboratory Medicine

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show abstract

“…Other studies found the same relationship and specifically confirmed the presence of CML in adipose tissue 17,18 . Taken together, it appears that CML is preferentially deposited in fat tissue and acts as an important mechanism involved in the dysregulation of adipokines in obesity, thereby contributing to the development of obesity-associated insulin resistance.…”

Section: Relationship Between Mid-gestational CML Glucose Indices Ansupporting

confidence: 61%

“…Thus, fat mass could influence circulating AGE concentrations through a role in the catabolism and breakdown of AGE. At the same time however, the CML/RAGE-axis appears to be a key modulator of obesity-induced dysregulation of adipokine expression in adipocytes and of subsequent insulin resistance 17 .…”

Section: Discussionmentioning

confidence: 99%

Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus

Bartáková¹,

Kollárová²,

Kuricová³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. The objective of the study was to measure one of the circulating Advanced Glycation End Products (AGEs) -Nε-(carboxymethyl)lysine (CML) -in a case-control study (n = 307) of pregnant women with gestational diabetes mellitus (GDM) and physiological pregnancies and to ascertain the factors contributing to CML levels and the potential relevance of CML for selected perinatal and postpartum outcomes. Methods. All subjects underwent oGTT between 24 th and 30 th week of gestation and GDM was diagnosed according to WHO criteria. CML was determined by ELISA using commercial kit. Results. Unadjusted and plasma protein adjusted CML levels were significantly higher in women with GDM compared to healthy controls (P = 0.00043 and P = 1x10 -5 , respectively, Mann-Whitney). CML was significantly inversely correlated with both pre-and mid-gestational BMI, however, differences between GDM and control group remained significant even after adjustment for BMI. CML levels correlated with 1-h and 2-h post-load glycaemia during oGTT. Conclusion. In conclusion, we found statistically significantly higher protein-and BMI-normalised CML levels measured during 24-30 th week of gestation in women with GDM compared to healthy pregnant controls. Further studies are warranted to comprehensively asses the spectrum of AGEs in GDM and their relevance to future metabolic health of mother and offspring.

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“…33 Nevertheless, these epidemiological studies do not encounter the underlying mechanism. Our present data provide a mechanistic explanation for these findings.…”

Section: /Leptrmentioning

confidence: 99%

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

Gaens

Goossens

Niessen

et al. 2014

ATVB

176

182

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Objective-Dysregulation of inflammatory adipokines by the adipose tissue plays an important role in obesity-associated insulin resistance. Pathways leading to this dysregulation remain largely unknown. We hypothesized that the receptor for advanced glycation end products (RAGE) and the ligand N ε -(carboxymethyl)lysine (CML) are increased in adipose tissue and, moreover, that activation of the CML-RAGE axis plays an important role in obesity-associated inflammation and insulin resistance. Approach and Results-In this study, we observed a strong CML accumulation and increased expression of RAGE in adipose tissue in obesity. We confirmed in cultured human preadipocytes that adipogenesis is associated with increased levels of CML and RAGE. Moreover, CML induced a dysregulation of inflammatory adipokines in adipocytes via a RAGE-dependent pathway. To test the role of RAGE in obesity-associated inflammation further, we constructed an obese mouse model that is deficient for RAGE (ie, RAGE . RAGE-mediated trapping in adipose tissue provides a mechanism underlying CML accumulation in adipose tissue and explaining decreased CML plasma levels in obese subjects. Decreased CML plasma levels in obese individuals were strongly associated with insulin resistance. endothelial cells, and macrophages. 9 RAGE is initially identified as the receptor for advanced glycation end products (AGEs), 10 but, in addition to AGEs, RAGE also interacts with multiple members of the proinflammatory S100/calgranulin family and high motility group box 1 protein. Conclusions-RAGE-mediated9,11 Binding of these ligands to RAGE leads to activation of signaling cascade and induction of nuclear factor-κB, which can subsequently lead to the production of inflammatory mediators.9,12 Therefore, the potential role of RAGE in the regulation of inflammation suggests that RAGE might be an important mechanism contributing to obesity-associated dysregulation of adipokines and development of insulin resistance. N ε -(carboxymethyl)lysine (CML) is a major AGE and is an important ligand for RAGE.10 CML is formed on proteins by nonenzymatic glycation and oxidation reactions. 13Alternative routes for CML formation have been described, including lipid peroxidation of polyunsaturated fatty acids.14,15 In fact, lipid peroxidation is a more important source for CML formation than glycoxidation reactions.14 Because of the reaction mechanism, CML formation is increased under hyperglycemic and hyperlipidemic conditions. The adipose tissue in obese conditions is characterized by increased levels of fatty acids, lipid peroxidation, and oxidative stress. Therefore, we can deduce that obesity is also a condition in which CML formation is increased and where CML can interact with RAGE. However, the role of CML-RAGE in obesity, obesity-associated inflammation, and insulin resistance has to date not been investigated.The aim of this study was to investigate the role of CML-RAGE axis in obesity-associated inflammation and insulin resistance. In the present study, we showed in huma...

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Fat Mass Is Inversely Associated with Serum Carboxymethyl-Lysine, An Advanced Glycation End Product, in Adults,

Cited by 63 publications

References 39 publications

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus

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

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Fat Mass Is Inversely Associated with Serum Carboxymethyl-Lysine, An Advanced Glycation End Product, in Adults,

Cited by 63 publications

References 39 publications

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus

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

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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