Phosphatidylethanolamine-N-methyltransferase Activity and Dietary Choline Regulate Liver-Plasma Lipid Flux and Essential Fatty Acid Metabolism in Mice

Watkins, Steven M.; Zhu, Xiaonan; Zeisel, Steven H.

doi:10.1093/jn/133.11.3386

Cited by 149 publications

(125 citation statements)

References 21 publications

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“…In the liver, the conversion of phospholipid from PE to PC (via SAMe and PEMT) is critical for DHA mobilization from the liver into the plasma (Figure 2). When this reaction does not occur normally, as seen in PEMT knockout mice (and possibly in folate deficiency), plasma concentrations of DHA are selectively decreased (Watkins et al, 2003). Since heavy alcohol intake may cause SAMe depletion in the liver (Lieber, 2000), folate availability may be especially critical for the creation of PC from PE in subjects who drink alcohol.…”

Section: Discussionmentioning

confidence: 99%

The relationship between folate and docosahexaenoic acid in men

et al. 2005

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Objective: Docosahexaenoic acid (DHA,, an essential omega 3 fatty acid, may protect against disorders of emotional regulation as well as cardiovascular disease. Animal studies demonstrate that dietary folate can increase tissue concentrations of DHA, although the literature, to date, includes no human studies examining the possibility that folate status may affect plasma DHA concentrations. The objective of this study is to determine if the blood concentrations of folate and DHA are correlated in humans. Design: Retrospective study. Setting: An American research hospital. Subjects: A total of 15 normal and 22 hostile and aggressive subjects, with a mean age of 38 years. Methods: Concentrations of plasma polyunsaturated essential fatty acids and red blood cell folate (RBC folate) were obtained prior to 1996, before American flour was enriched with folate. Results: RBC folate was significantly correlated with plasma DHA, r ¼ 0.57, P ¼ 0.005 in the aggressive group. Age, smoking and alcohol consumption did not alter the results. No other essential fatty acids were significantly associated with RBC folate in either group. Conclusions: The positive relationship between plasma DHA and RBC folate concentrations suggests that these two nutrients should be examined together in order to make the most accurate inferences about their relative contributions to disease pathogenesis. Our findings present one explanation why some conditions associated with hostility and low DHA status, such as cardiovascular disease and emotional disorders, are also associated with low folate status.

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Section: Discussionmentioning

confidence: 99%

The relationship between folate and docosahexaenoic acid in men

et al. 2005

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“…Recent work in PEMT-deficient mice has revealed promising results for benefits of choline supplementation. Namely, PEMTdeficient mice develop severe steatosis with both a cholinedeficient diet and a regular chow diet [35]. However, levels of liver TGs significantly decrease when these mice are supplemented with choline.…”

Section: Animal Studiesmentioning

confidence: 99%

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

Duric

Sivanesan

Bakovic

2012

Euro J Lipid Sci & Tech

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Non‐alcoholic fatty liver disease (NAFLD) is the most common liver condition in the developed world and may progress to more severe forms of disease such as cirrhosis or liver cancer. Thus, steps taken to reduce its prevalence through preventative nutritional approaches such as functional foods and nutraceuticals (FFN) should be pursued. It is well known that certain lipotropic nutrients such as choline and metabolites betaine and phosphatidylcholine (PC; lecithin) could prevent or alleviate fatty liver through a variety of mechanisms, including increased hepatic VLDL secretion. Animal and human studies have demonstrated clear protective effects of choline, betaine and PC for NAFLD as well as possible roles in CVD prevention from epidemiological data. Currently, choline consumption is below dietary recommendations due in large part to a general lack of understanding regarding the importance of this nutrient for human health. As lecithin is commonly added (in small amounts) in many processed foods due to its functional capabilities, it is projected that increasing its abundance in the food supply and increasing consumer education and acceptance of lecithin‐based functional foods and nutraceuticals may represent a progressive step towards preventing liver and whole‐body metabolic pathologies in many areas of the world.

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“…However, regulation of CT activity has also been implicated in many other biological processes, including neurite growth (50), neural tube closure (51), and fetal development (52). It has also been suggested that dysregulation of hepatic PC biosynthesis disrupts the distribution of long chain polyunsaturated fatty acids in liver and plasma (53).…”

Section: Figmentioning

confidence: 99%

Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins

Jacobs

Devlin

Tabas

et al. 2004

Journal of Biological Chemistry

166

178

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CTP:phosphocholine cytidylyltransferase (CT) is the key regulatory enzyme in the CDP-choline pathway for the biosynthesis of phosphatidylcholine. Hepatic cells express both an ␣ and a ␤2 isoform of CT and can also synthesize phosphatidylcholine via the sequential methylation of phosphatidylethanolamine catalyzed by phosphatidylethanolamine N-methyltransferase. To ascertain the functional importance of CT␣, we created a mouse in which the hepatic CT␣ gene was specifically inactivated by the Cre/LoxP procedure. In CT␣ knockout mice, hepatic CT activity (due to residual CT␤2 activity as well as activity in nonhepatic cells) was 15% of normal, whereas phosphatidylethanolamine N-methyltransferase activity was elevated 2-fold compared with controls. Lipid analyses of the liver indicated that female knockout mice had reduced phosphatidylcholine levels and accumulated triacylglycerols. The plasma phosphatidylcholine concentration was reduced in the CT␣ knockout (independent of gender), as were levels of high density lipoproteins (cholesterol and apoAI) and very low density lipoproteins (triacylglycerols and apoB100). Experiments in which mice were injected with Triton WR1339 indicated that apoB secretion was decreased in hepatic-specific CT␣ knockout mice compared with controls. These results suggest an important role for hepatic CT␣ in regulating both hepatic and systemic lipid and lipoprotein metabolism.

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Phosphatidylethanolamine-N-methyltransferase Activity and Dietary Choline Regulate Liver-Plasma Lipid Flux and Essential Fatty Acid Metabolism in Mice

Cited by 149 publications

References 21 publications

The relationship between folate and docosahexaenoic acid in men

The relationship between folate and docosahexaenoic acid in men

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins

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