PMID- 21412218
OWN - NLM
STAT- MEDLINE
DCOM- 20111229
LR  - 20171116
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 80
IP  - 2
DP  - 2011 Jul
TI  - Targeted reduction of advanced glycation improves renal function in obesity.
PG  - 190-8
LID - 10.1038/ki.2011.57 [doi]
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.
FAU - Harcourt, Brooke E
AU  - Harcourt BE
AD  - Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria, Australia. 
      brooke.harcourt@bakeridi.edu.au
FAU - Sourris, Karly C
AU  - Sourris KC
FAU - Coughlan, Melinda T
AU  - Coughlan MT
FAU - Walker, Karen Z
AU  - Walker KZ
FAU - Dougherty, Sonia L
AU  - Dougherty SL
FAU - Andrikopoulos, Sofianos
AU  - Andrikopoulos S
FAU - Morley, Amy L
AU  - Morley AL
FAU - Thallas-Bonke, Vicki
AU  - Thallas-Bonke V
FAU - Chand, Vibhasha
AU  - Chand V
FAU - Penfold, Sally A
AU  - Penfold SA
FAU - de Courten, Maximilian P J
AU  - de Courten MP
FAU - Thomas, Merlin C
AU  - Thomas MC
FAU - Kingwell, Bronwyn A
AU  - Kingwell BA
FAU - Bierhaus, Angelika
AU  - Bierhaus A
FAU - Cooper, Mark E
AU  - Cooper ME
FAU - de Courten, Barbora
AU  - de Courten B
FAU - Forbes, Josephine M
AU  - Forbes JM
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110316
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Thiazoles)
RN  - DGH49JXB1F (alagebrium)
SB  - IM
CIN - Kidney Int. 2011 Jul;80(2):133-5. PMID: 21720304
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Cross-Over Studies
MH  - Diet
MH  - Glycation End Products, Advanced/administration & dosage/*adverse effects
MH  - Humans
MH  - Inflammation/prevention & control
MH  - Kidney/drug effects/*physiopathology
MH  - Kidney Diseases/chemically induced/*diet therapy/drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Obesity/*diet therapy/drug therapy/*physiopathology
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/deficiency/*drug effects
MH  - Thiazoles/pharmacology/therapeutic use
MH  - Young Adult
EDAT- 2011/03/18 06:00
MHDA- 2011/12/30 06:00
CRDT- 2011/03/18 06:00
PHST- 2011/03/18 06:00 [entrez]
PHST- 2011/03/18 06:00 [pubmed]
PHST- 2011/12/30 06:00 [medline]
AID - S0085-2538(15)55018-7 [pii]
AID - 10.1038/ki.2011.57 [doi]
PST - ppublish
SO  - Kidney Int. 2011 Jul;80(2):190-8. doi: 10.1038/ki.2011.57. Epub 2011 Mar 16.