Choline is an essential nutrient, in the liver it is a precursor necessary for the synthesis of phosphatidylcholine (PC) and is also required as a methyl donor towards the synthesis of betaine and later regeneration of S-adenomethionine (SAM). Choline deficiency is known to trigger the development of non-alcoholic fatty liver disease and affect mitochondrial homeostasis along with a myriad of methylation related regulatory mechanisms. Because of its importance in maintaining liver lipid and mitochondrial homeostasis, choline metabolism has been well characterized with the exception of its transport. The identification of choline transporters has only been recently discovered and because of this, relatively little is known about their expression and regulation. This study has established that choline transporter like proteins 1-5 (CTL1-5) is an intermediate affinity transport system responsible for ~80% of hepatic choline uptake with a smaller percentage accomplished through the low affinity organic cation transporter 1-3/N1-2 (OCT1-3/N1-2) transporters. SLC44A1 expression and choline incorporation have been shown to follow a 24 hour rhythmic trend suggesting the presence of a circadian regulatory mechanism. This finding is supported by the significant decrease in choline expression and aberrant pattern of choline incorporation discovered among rhythmic deficient BMAL-/- mice and through a bioinformatics analysis which revealed the existence of four REV-ERBα consensus sequences. Hepatic SLC44A1 expression and choline incorporation have also been shown to decrease with the onset of obesity. Choline uptake was also shown to decrease following treatment with the free fatty acid oleate. This work increases our knowledge of hepatic choline transport and demonstrates a link between the circadian rhythm and obesity with the hepatic CTL1 transporter.

: Choline is being used in all mammalian cells as a precursor for synthesis of a major phospholipide phosphatidylcholine and as a donor of acetyl residues. Cholinergic neurons in addition require choline to synthesize neuromediator acetylcholine. The ability of cells to create choline via de novo synthesis is limited and therefore they need to transport choline from extracellular space. Limited availability of choline in brain leads specifically to diminished function of cholinergic neurons and in general to impaired reparation of biological membranes. Dysfunctions of cholinergic signaling in brain is characteristic for Alzheimer's disease. Aim of this work was to investigate whether gene and protein expression of high- affinity cholinergic transporters is altered in 5-6 months old APPswe/PS1dE9 mouse model of Alzheimer's disease. Expression of specific high-affinity cholinergic transporter CHT1 (responsible for transport of choline to be used for acetylcholine synthesis) and putative high-afinity choline transporter CTL1 (generally present in all cells and related to high affinity choline transport for phospholipide synthesis) in cerebral cortex was measured. Compared to non-trangenic littermates, no changes in the expression of both genes were detected at either mRNA (quantitative PCR) or protein...