Tissue-specific alterations of methyl group metabolism with DNA hypermethylation in the Zucker (type 2) diabetic fatty rat.
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The Department of Food Science and Human Nutrition (FSHN) at Iowa State University is jointly administered by the Colleges of Agriculture and Life Sciences and Human Science. FSHN combines the study and practical application of food sciences and technology with human nutrition in preparation for a variety of fields including: the culinary sciences, dietetics, nutrition, food industries, and diet and exercise.
History
The department was established in 1991 through the merging of the Department of Food Sciences and Technology (of the College of Agriculture), and the Department of Food and Nutrition (of the College of Family and Consumer Sciences).
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- College of Agriculture and Life Sciences (parent college)
- College of Human Sciences (parent college)
- Department of Human Nutrition (predecessor, 1990)
- Department of Food Sciences and Nutrition (predecessor, 1990)
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Abstract
BackgroundAltered methyl group and homocysteine metabolism were tissue-specific, persistent, and preceded hepatic DNA hypomethylation in type 1 diabetic rats. Similar metabolic perturbations have been shown in the Zucker (type 2) diabetic fatty (ZDF) rat in the pre-diabetic and early diabetic stages, but tissue specificity and potential impact on epigenetic marks are unknown, particularly during pathogenesis.
Methods ZDF (fa/fa) and lean (+/?) control rats were killed at 12 and 21 weeks of age, representing early and advanced diabetic conditions. Blood and tissues were analysed with respect to methyl group and homocysteine metabolism, including DNA methylation.
Results At 12 weeks, hepatic glycine N-methyltransferase (GNMT), methionine synthase, and cystathionine β-synthase (CBS) activity and/or abundance were increased in ZDF rats. At 21 weeks, GNMT activity was increased in liver and kidney; however, only hepatic CBS protein abundance (12 weeks) and betaine-homocysteine S-methyltransferase mRNA expression (21 weeks) were significantly elevated (78 and 100%, respectively). Hepatic phosphatidylethanolamine N-methyltransferase expression was also elevated in the ZDF rat. Homocysteine concentrations were decreased in plasma and kidney, but not in liver, at 12 and 21 weeks. In contrast to hepatic DNA hypomethylation in the type 1 diabetic rat, genomic DNA was hypermethylated at 12 and 21 weeks in the liver of ZDF rats, concomitant with an increase in DNA methyltransferase 1 expression at 21 weeks.
ConclusionsThe pathogenesis of type 2 diabetes in the ZDF rat was associated with tissue and disease stage-specific aberrations of methyl group and homocysteine metabolism, with persistent hepatic global DNA hypermethylation.
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This is the peer reviewed version of the following article is from Diabetes / Metabolism Research and Reviews, February 2012, 28(2); 123-131. Which has been published in final form at Doi: 10.1002/dmrr.1281. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.