In:
Nephron, S. Karger AG, Vol. 144, No. 8 ( 2020), p. 400-412
Abstract:
〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Alström syndrome is a rare recessive genetic disease caused by mutations in 〈 i 〉 ALMS1 〈 /i 〉 , which encodes a protein that is related to cilia function and intracellular endosome trafficking. The syndrome has been linked to impaired glucose metabolism and CKD. Polymorphisms in 〈 i 〉 Alms1 〈 /i 〉 have likewise been linked to CKD, but little is known about the modification of the phenotype by environmental factors. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 To gain further insights, the fat aussie ( 〈 i 〉 foz 〈 /i 〉 ) mouse strain, a genetic murine model of Alström syndrome, was exposed to a normal chow (NC) or to a Western diet (WD, 20% fat, 34% sucrose by weight, and 0.2% cholesterol) and renal outcomes were measured. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Body weight and albuminuria were higher in 〈 i 〉 foz 〈 /i 〉 than in wild-type (WT) mice on both diets but WD significantly increased the difference. Measurement of plasma creatinine and cystatin C indicated that glomerular filtration rate was preserved in 〈 i 〉 foz 〈 /i 〉 versus WT independent of diet. Renal markers of injury, inflammation, and fibrosis were similar in both genotypes on NC but significantly greater in 〈 i 〉 foz 〈 /i 〉 than in WT mice on WD. A glucose tolerance test performed in 〈 i 〉 foz 〈 /i 〉 and WT mice on WD revealed similar basal blood glucose levels and subsequent blood glucose profiles. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 WD sensitizes a murine model of Alström syndrome to kidney injury, inflammation, and fibrosis, an effect that may not be solely due to effects on glucose metabolism. Polymorphisms in 〈 i 〉 Alms1 〈 /i 〉 may induce CKD in part by modulating the deleterious effects of high dietary fat and sucrose on kidney outcome.
Type of Medium:
Online Resource
ISSN:
1660-8151
,
2235-3186
Language:
English
Publisher:
S. Karger AG
Publication Date:
2020
detail.hit.zdb_id:
2810853-X
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