Targeted reduction of advanced glycation improves renal function in obesity

Abstract

Obesity is highly prevalent in Western populations and is considered a risk factor for the development of renal impairment. Interventions that reduce the tissue burden of advanced glycation end-products (AGEs) have shown promise in stemming the progression of chronic disease. Here we tested if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction. Overweight and obese individuals (body mass index (BMI) 26-39 kg/m(2)) were recruited to a randomized, crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet. Renal function and an inflammatory profile (monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF)) were improved following the low-AGE diet. Mechanisms of advanced glycation-related renal damage were investigated in a mouse model of obesity using the AGE-lowering pharmaceutical, alagebrium, and mice in which the receptor for AGE (RAGE) was deleted. Obesity, resulting from a diet high in both fat and AGE, caused renal impairment; however, treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion, creatinine clearance, the inflammatory profile, and renal oxidative stress. Alagebrium treatment, however, resulted in decreased weight gain and improved glycemic control compared with wild-type mice on a high-fat Western diet. Thus, targeted reduction of the advanced glycation pathway improved renal function in obesity.

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

“…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.…”

“…We and others have demonstrated that the consumption of diets high in AGEs elicit deleterious effects throughout the body including: increased inflammation [14,15] driving insulin resistance [16] and impairing renal function [14,17,18].…”

Skin Autofluorescence and the Association with Renal and Cardiovascular Risk Factors in Chronic Kidney Disease Stage 3

“…Thus, it is possible that the mechanisms contributing to the development of proteinuria also provoke AGE formation and accumulation, or that AGE exacerbate proteinuria. A role for AGE in the pathogenesis of proteinuria is suggested by a study that observed a significant reduction in albuminura after 2 weeks of a low AGE diet in 11 overweight and obese individuals (48).…”

“…These observations are important because factors such as diet and smoking are potentially modifiable. A recent study has reported a reduction in albuminuria and plasma levels of the proinflammatory cytokine monocyte chemotactic protein-1 in overweight and obese participants after just 2 weeks of a low-AGE diet (48).…”

Formação de produtos da reação de Maillard em carne bovina (<i>Semimembranosus</i>) submetida a diferentes técnicas de cocção

“…A ingestão de substâncias formadas pela RM nos alimentos está correlacionada com o aumento de níveis séricos de AGEs em humanos URIBARRI et al, 2005;POULSEN et al, 2013), e, ensaios clínicos obtiveram benefícios com a restrição de PRM na dieta: tanto em pacientes com diabetes tipo 2 como em indivíduos saudáveis foram observados a diminuição do stress oxidativo, a diminuição de marcadores inflamatórios, melhora de marcadores da resistência a insulina e de disfunção vascular, e diminuição dos níveis séricos de AGEs (DELGADO-ANDRADE et al, 2007;URIBARRI et al, 2010;BIRLOUEZ-ARAGON et al, 2010;CHAO et al, 2010;HARCOURT et al, 2011).…”