Targeted reduction of advanced glycation improves renal function in obesity

Brooke E Harcourt; Karly C Sourris; Melinda T Coughlan; Karen Z Walker; Sonia L Dougherty; Sofianos Andrikopoulos; Amy L Morley; Vicki Thallas-Bonke; Vibhasha Chand; Sally A Penfold; Maximilian P J de Courten; Merlin C Thomas; Bronwyn A Kingwell; Angelika Bierhaus; Mark E Cooper; Barbora de Courten; Josephine M Forbes

doi:10.1038/ki.2011.57

Targeted reduction of advanced glycation improves renal function in obesity

Brooke E Harcourt, Karly C Sourris, Melinda T Coughlan, Karen Z Walker, Sonia L Dougherty, Sofianos Andrikopoulos, Amy L Morley, Vicki Thallas-Bonke, Vibhasha Chand, Sally A Penfold, Maximilian P J de Courten, Merlin C Thomas, Bronwyn A Kingwell, Angelika Bierhaus, Mark E Cooper, Barbora de Courten, Josephine M Forbes

80 Citations (Scopus)

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.

Original language	English
Journal	Kidney International
Volume	80
Issue number	2
Pages (from-to)	190-8
Number of pages	9
ISSN	0085-2538
DOIs	https://doi.org/10.1038/ki.2011.57
Publication status	Published - 2 Jul 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ki.2011.57

Cite this

Harcourt, B. E., Sourris, K. C., Coughlan, M. T., Walker, K. Z., Dougherty, S. L., Andrikopoulos, S., Morley, A. L., Thallas-Bonke, V., Chand, V., Penfold, S. A., de Courten, M. P. J., Thomas, M. C., Kingwell, B. A., Bierhaus, A., Cooper, M. E., Courten, B. D., & Forbes, J. M. (2011). Targeted reduction of advanced glycation improves renal function in obesity. Kidney International, 80(2), 190-8. https://doi.org/10.1038/ki.2011.57

Harcourt, BE, Sourris, KC, Coughlan, MT, Walker, KZ, Dougherty, SL, Andrikopoulos, S, Morley, AL, Thallas-Bonke, V, Chand, V, Penfold, SA, de Courten, MPJ, Thomas, MC, Kingwell, BA, Bierhaus, A, Cooper, ME, Courten, BD & Forbes, JM 2011, 'Targeted reduction of advanced glycation improves renal function in obesity', Kidney International, vol. 80, no. 2, pp. 190-8. https://doi.org/10.1038/ki.2011.57

@article{dfad6e996cf346adbad2b2b66ed3fdcf,

title = "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.",

author = "Harcourt, {Brooke E} and Sourris, {Karly C} and Coughlan, {Melinda T} and Walker, {Karen Z} and Dougherty, {Sonia L} and Sofianos Andrikopoulos and Morley, {Amy L} and Vicki Thallas-Bonke and Vibhasha Chand and Penfold, {Sally A} and {de Courten}, {Maximilian P J} and Thomas, {Merlin C} and Kingwell, {Bronwyn A} and Angelika Bierhaus and Cooper, {Mark E} and Courten, {Barbora de} and Forbes, {Josephine M}",

year = "2011",

month = jul,

day = "2",

doi = "10.1038/ki.2011.57",

language = "English",

volume = "80",

pages = "190--8",

journal = "Kidney International",

issn = "0085-2538",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - Targeted reduction of advanced glycation improves renal function in obesity

AU - Harcourt, Brooke E

AU - Sourris, Karly C

AU - Coughlan, Melinda T

AU - Walker, Karen Z

AU - Dougherty, Sonia L

AU - Andrikopoulos, Sofianos

AU - Morley, Amy L

AU - Thallas-Bonke, Vicki

AU - Chand, Vibhasha

AU - Penfold, Sally A

AU - de Courten, Maximilian P J

AU - Thomas, Merlin C

AU - Kingwell, Bronwyn A

AU - Bierhaus, Angelika

AU - Cooper, Mark E

AU - Courten, Barbora de

AU - Forbes, Josephine M

PY - 2011/7/2

Y1 - 2011/7/2

N2 - 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.

AB - 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.

U2 - 10.1038/ki.2011.57

DO - 10.1038/ki.2011.57

M3 - Journal article

C2 - 21412218

SN - 0085-2538

VL - 80

SP - 190

EP - 198

JO - Kidney International

JF - Kidney International

IS - 2

ER -

Targeted reduction of advanced glycation improves renal function in obesity

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this