Title |
Targeted reduction of advanced glycation improves renal function in obesity
|
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Published in |
Kidney International, March 2011
|
DOI | 10.1038/ki.2011.57 |
Pubmed ID | |
Authors |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Spain | 1 | <1% |
United States | 1 | <1% |
Unknown | 132 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 22 | 16% |
Student > Ph. D. Student | 19 | 14% |
Student > Bachelor | 17 | 13% |
Researcher | 13 | 10% |
Professor | 10 | 7% |
Other | 27 | 20% |
Unknown | 26 | 19% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 34 | 25% |
Agricultural and Biological Sciences | 19 | 14% |
Nursing and Health Professions | 11 | 8% |
Biochemistry, Genetics and Molecular Biology | 10 | 7% |
Psychology | 6 | 4% |
Other | 24 | 18% |
Unknown | 30 | 22% |