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Permanent link (DOI): https://doi.org/10.7939/R3NK36J88

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Impaired de novo choline synthesis explains why phosphatidylethanolamine N-methyltransferase-deficient mice are protected from diet-induced obesity Open Access

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Author or creator
Jacobs, René L.
Zhao, Yang
Koonen, Debby P. Y.
Sletten, Torunn
Su, Brian
Lingrell, Susanne
Cao, Guoqing
Peake, David A.
Kuo, Ming-Shang
Proctor, Spencer D.
Kennedy, Brian P.
Dyck, Jason R. B.
Vance, Dennis E.
Additional contributors
Subject/Keyword
Diabetes
Choline
Phospholipid Metabolism
Methylation
Phosphatidylcholine
Adipose Tissue
Metabolism
Type of item
Journal Article (Published)
Language
English
Place
Time
Description
Phosphatidylcholine (PC) is synthesized from choline via the CDP-choline pathway. Liver cells can also synthesize PC via the sequential methylation of phosphatidylethanolamine, catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). The current study investigates whether or not hepatic PC biosynthesis is linked to diet-induced obesity. Pemt+/+ mice fed a high fat diet for 10 weeks increased in body mass by 60% and displayed insulin resistance, whereas Pemt−/− mice did not. Compared with Pemt+/+ mice, Pemt−/− mice had increased energy expenditure and maintained normal peripheral insulin sensitivity; however, they developed hepatomegaly and steatosis. In contrast, mice with impaired biosynthesis of PC via the CDP-choline pathway in liver became obese when fed a high fat diet. We, therefore, hypothesized that insufficient choline, rather than decreased hepatic phosphatidylcholine, was responsible for the lack of weight gain in Pemt−/− mice despite the presence of 1.3 g of choline/kg high fat diet. Supplementation with an additional 2.7 g of choline (but not betaine)/kg of diet normalized energy metabolism, weight gain, and insulin resistance in high fat diet-fed Pemt−/− mice. Furthermore, Pemt+/+ mice that were fed a choline-deficient diet had increased oxygen consumption, had improved glucose tolerance, and gained less weight. Thus, de novo synthesis of choline via PEMT has a previously unappreciated role in regulating whole body energy metabolism.
Date created
2010
DOI
doi:10.7939/R3NK36J88
License information
© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
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Citation for previous publication
Jacobs, R. L., Zhao, Y., Koonen, D. P. Y., Sletten, T., Su, B., Lingrell, S., Cao, G., Peake, D. A., Kuo, M. S., Proctor, S. D., Kennedy, B. P., Dyck, J. R. B., & Vance, D. E. (2010). Impaired de novo choline synthesis explains why phosphatidylethanolamine N-methyltransferase-deficient mice are protected from diet-induced obesity. Journal of Biological Chemistry, 285(29), 22403-22413.  http://dx.doi.org/10.1074/jbc.M110.108514

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