看片视频


Diet-induced obesity and kidney disease - In search of a susceptible mouse
model.
Authors Wicks SE, Nguyen TT, Breaux C, Kruger C, Stadler K
Submitted By Krisztian Stadler on 11/30/2015
Status Published
Journal Biochimie
Year 2015
Date Published 8/1/2015
Volume : Pages Not Specified : Not Specified
PubMed Reference
Abstract Obesity and metabolic syndrome are independent risk factors for chronic kidney
disease, even without diabetes or hyperglycemia. Here, we compare two mouse
models that are susceptible to diet-induced obesity: the relatively renal injury
resistant C57BL/6J strain and the DBA2/J strain which is more sensitive to renal
injury. Our studies focused on characterizing the effects of high fat diet
feeding on renal oxidative stress, albuminuria, fibrosis and podocyte
loss/insulin resistance. While the C57BL/6J strain does not develop significant
pathological changes in the kidney, at least on lard based diets within the time
frame investigated, it does show increased renal iNOS and nitrotyrosine levels
and elevated mitochondrial respiration which may be indicative of mitochondrial
lipid overfueling. Restricting the high fat diet to decrease adiposity decreased
the levels of cellular oxidative stress markers, indicating that
adiposity-related proinflammatory changes such as increased iNOS levels may
trigger similar responses in the kidney. Mitochondrial respiration remained
higher, suggesting that eating excess lipids, despite normal adiposity may still
lead to renal mitochondrial overfueling. In comparison, DBA/2J mice developed
albuminuria on similar diets, signs of fibrosis, oxidative stress, early signs
of podocyte loss (evaluated by the markers podocin and WT-1) and podocyte
insulin resistance (unable to phosphorylate their glomerular Akt when insulin
was given). To summarize, while the C57BL/6J strain is not particularly
susceptible to renal disease, changes in its mitochondrial lipid handling
combined with the easy availability of transgenic technology may be an advantage
to design new knockout models related to mitochondrial lipid metabolism. The
DBA/2J model could serve as a basis for studying podocyte insulin resistance and
identifying early renal markers in obesity before more severe kidney disease
develops. Based on our observations, we encourage further critical evaluation of
mouse models for obesity related chronic kidney disease.

Complications