Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 129, Issue 4, Pages 201-206Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2007.12.009
Keywords
progeriod syndrome; Werner's syndrome; high fat and sugar diet; type 2 diabetes; obesity
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Funding
- NCI NIH HHS [P01CA77852, P01 CA077852, P01 CA077852-109003] Funding Source: Medline
- NIEHS NIH HHS [U01 ES011045-05S1, U01 ES011045-05, U01 ES011045, U01ES11045] Funding Source: Medline
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Werner syndrome (WS) is an autosomal recessive progeroid syndrome caused by mutations in the Werner (Wrn) gene. WS patients have increased incidence of a number of chronic conditions including insulin resistance and type 2 diabetes. Since ingestion of foods that are high in fat and sugar is associated with increased incidence of diabetes, we examined if Wrn mutations might affect metabolic response to a diabetogenic diet. Four-month-old mice with a null mutation for the Wrn gene were fed a diet consisting of 36% fat (lard), 33% table sugar, and 20% protein plus balanced vitamins and minerals. Wrn null mice had significantly increased body weights, increased serum insulin levels, impaired glucose tolerance, and insulin resistance during 4 months of eating the diabetogenic diet. Diffuse fatty infiltration of the liver and pancreatic islet hyperplasia was characteristic morphological features. These observations suggest that Wrn null mice have impaired glucose homeostasis and fat metabolism, and may be a useful model to investigate metabolic conditions associated with aging. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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