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

• Author(s) / Creator(s)

  • Kuo, Ming-Shang
  • Dyck, Jason R. B.
  • Sletten, Torunn
  • Proctor, Spencer D.
  • Jacobs, René L.
  • Lingrell, Susanne
  • Cao, Guoqing
  • Peake, David A.
  • Kennedy, Brian P.
  • Zhao, Yang
  • Vance, Dennis E.
  • Koonen, Debby P. Y.
  • Su, Brian

• 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

• Subjects / Keywords

  • Phosphatidylcholine
  • Methylation
  • Phospholipid Metabolism
  • Choline
  • Metabolism
  • Adipose Tissue
  • Diabetes

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/R3NK36J88

• License

  © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.