Thematic Review Series: Glycerolipids. Phosphatidylcholine and choline homeostasis

Li, Zhaoyu; Vance, Dennis E.

doi:10.1194/jlr.r700019-jlr200

Cited by 529 publications

(257 citation statements)

References 96 publications

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“…In contrast to the present study, the plasma TAG concentrations were reduced in the mice fed the experimental diet despite the high fat and cholesterol levels (41). Choline is required for cell signalling and VLDL secretion from hepatocytes (42). Dietary choline as well as phosphatidylcholine has been shown to affect hepatic cholesterol homeostasis in rats, including increased excretion of cholesterol via the bile (43,44).…”

Section: Discussioncontrasting

confidence: 53%

Dietary herring improves plasma lipid profiles and reduces atherosclerosis in obese low-density lipoprotein receptor-deficient mice

Gabrielsson

Wikström²,

Jakubowicz³

et al. 2011

Int J Mol Med

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Abstract. Diet is a significant modifiable risk factor for cardiovascular disease and high fish intake has been associated with vascular health in population studies. However, intervention studies have been inconclusive. In this study, male low-density lipoprotein receptor-deficient mice were given 16-week high fat/high sucrose diets, supplemented with either minced herring fillets or minced beef. The diets were matched in total fat and cholesterol content; taurine content and fatty acid composition was analysed. Body weights were recorded throughout the study; plasma lipids were analysed at week 8 and 16. Body composition and adipocyte size were evaluated at study end. Atherosclerosis was evaluated at week 12 (ultrasound) and at termination (en face histology). Herring-fed mice had a higher proportion of long-chain n-3 polyunsaturated fatty acids in the hepatic triacylglycerides (TAG) and phospholipid fractions. The herring-fed mice had increased body weight (P= 0.007), and reduced epididymal adipocyte size (P= 0.009), despite similar food intake and body composition as the beef-fed mice. The herring-fed mice had lower plasma TAG and verylow-density lipoprotein (VLDL)-cholesterol concentrations throughout the study (TAG; P= 0.0012 and 0.004, VLDLcholesterol; P=0.006 and 0.041, week 8 and 16, respectively). At week 16, the herring-fed had higher plasma concentrations of HDL-cholesterol (P=0.004) and less atherosclerotic lesions in the aortic arch (P=0.007) compared with the beef-fed mice.In conclusion, dietary herring in comparison to beef markedly improved vascular health in this mouse model, suggesting that herring provides an added value beyond its content of macronutrients.

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Section: Discussioncontrasting

confidence: 53%

Dietary herring improves plasma lipid profiles and reduces atherosclerosis in obese low-density lipoprotein receptor-deficient mice

Gabrielsson

Wikström²,

Jakubowicz³

et al. 2011

Int J Mol Med

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“…Indeed, previous findings in PE methyltransferase knock-out mice fed a CD diet resulted in steatohepatitis due to low plasma membrane PC/PE ratio, which contributed to disrupted membrane integrity and decreased membrane fluidity (31). The observed outcome is intriguing as unlike MCD diet the MD diet contains an adequate choline level, which would be expected to drive the CDP-choline branch of the Kennedy pathway to synthesize PC de novo (11,32), although the PC synthesis from PE methylation would be predicted to be impaired due to the limitation of SAM. To account for this unexpected finding (decreased PC/PE ratio despite choline in the MD group), we observed that methionine deficiency increased hepatic ceramide levels in agreement with previous observations in PC12 cells (35) and in mice fed the MCD diet (37).…”

Section: Discussionmentioning

confidence: 90%

Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis

Caballero¹,

Fernández²,

Matías³

et al. 2010

Journal of Biological Chemistry

222

174

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The pathogenesis and treatment of nonalcoholic steatohepatitis (NASH) are not well established. Feeding a diet deficient in both methionine and choline (MCD) is one of the most common models of NASH, which is characterized by steatosis, mitochondrial dysfunction, hepatocellular injury, oxidative stress, inflammation, and fibrosis. However, the individual contribution of the lack of methionine and choline in liver steatosis, advanced pathology and impact on mitochondrial S-adenosyl-Lmethionine (SAM) and glutathione (GSH), known regulators of disease progression, has not been specifically addressed. Here, we examined the regulation of mitochondrial SAM and GSH and signs of disease in mice fed a MCD, methionine-deficient (MD), or choline-deficient (CD) diet. The MD diet reproduced most of the deleterious effects of MCD feeding, including weight loss, hepatocellular injury, oxidative stress, inflammation, and fibrosis, whereas CD feeding was mainly responsible for steatosis, characterized by triglycerides and free fatty acids accumulation. These findings were preceded by MCD-or MD-mediated SAM and GSH depletion in mitochondria due to decreased mitochondrial membrane fluidity associated with a lower phosphatidylcholine/phosphatidylethanolamine ratio. MCD and MD but not CD feeding resulted in increased ceramide levels by acid sphingomyelinase. Moreover, GSH ethyl ester or SAM therapy restored mitochondrial GSH and ameliorated hepatocellular injury in mice fed a MCD or MD diet. Thus, the depletion of SAM and GSH in mitochondria is an early event in the MCD model of NASH, which is determined by the lack of methionine. Moreover, therapy using permeable GSH prodrugs may be of relevance in NASH.

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“…hyde is primarily formed through the mitochondrial oxidation of choline in the liver and kidney (47,48); hence, mitochondrial ALDH7A1 localization in liver and kidney is consistent with its role in betaine synthesis. To date, ALDH9A1 is the only other ALDH enzyme known to metabolize this substrate (1).…”

Section: Discussionmentioning

confidence: 93%

Aldehyde Dehydrogenase 7A1 (ALDH7A1) Is a Novel Enzyme Involved in Cellular Defense against Hyperosmotic Stress

Brocker

Lassen

Estey

et al. 2010

Journal of Biological Chemistry

172

163

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Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. Human ALDH7A1 expression in Chinese hamster ovary cells attenuated osmotic stress-induced apoptosis caused by increased extracellular concentrations of sucrose or sodium chloride. Purified recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates, including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, ␣-aminoadipic semialdehyde. The crystal structure for ALDH7A1 supports the enzyme's substrate specificities. Tissue distribution studies in mice showed the highest expression of ALDH7A1 protein in liver, kidney, and brain, followed by pancreas and testes. ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria, making it unique among the aldehyde dehydrogenase enzymes. Analysis of human and mouse cDNA sequences revealed mitochondrial and cytosolic transcripts that are differentially expressed in a tissue-specific manner in mice. In conclusion, ALDH7A1 is a novel aldehyde dehydrogenase expressed in multiple subcellular compartments that protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. The human aldehyde dehydrogenase (ALDH)3 superfamily contains 19 enzymes involved in the NAD(P)ϩ -dependent oxidation of aldehydes to their corresponding carboxylic acids. These enzymes play crucial roles in a number of physiological processes by efficiently metabolizing a wide array of endogenous and exogenous aldehydes (1). Aldehydes are highly reactive molecules that can form adducts resulting in DNA damage and enzyme inactivation. As such, their removal is of the utmost importance. ALDH enzymes also couple the removal of these potentially toxic aldehydes to NAD(P)H production, which, in turn, helps maintain cellular redox balance. Finally, ALDH activity generates a number of important cellular molecules, including retinoic acid, the neurotransmitter ␥-aminobutyric acid, the major dietary folate tetrahydrofolate, and the osmolyte betaine (1).Human ALDH7A1 was originally identified as sharing 60% homology with the osmotic stress-induced 26g pea turgor protein (according to the official nomenclature now referred to as ALDH7B1), found in the common garden pea (Pisum sativum) (2). Initially named "antiquitin," the ALDH7A1 protein has been highly conserved throughout evolution. Indeed, the degree of homology noted between ALDH7A1 and ALDH7B1 is comparable with that observed between the human and pea histone H2A proteins, which are among the most evolutionarily conserved of all eukaryotic proteins (2, 3). Such a high degree of sequence similarity between species ofte...

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Thematic Review Series: Glycerolipids. Phosphatidylcholine and choline homeostasis

Cited by 529 publications

References 96 publications

Dietary herring improves plasma lipid profiles and reduces atherosclerosis in obese low-density lipoprotein receptor-deficient mice

Dietary herring improves plasma lipid profiles and reduces atherosclerosis in obese low-density lipoprotein receptor-deficient mice

Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis

Aldehyde Dehydrogenase 7A1 (ALDH7A1) Is a Novel Enzyme Involved in Cellular Defense against Hyperosmotic Stress

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