Document Type

Article

Publication Date

7-24-2025

Comments

This article is the author’s final published version in International Journal of Molecular Sciences, Volume 26, Issue 15, 2025, Article number 7159.

The published version is available at https://doi.org/10.3390/ijms26157159. Copyright 2025 by the authors.

Abstract

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport systems (high-affinity and low-affinity choline transporters) with distinct features and roles. An adequate dietary intake of choline during pregnancy supports proper fetal development, and throughout life supports brain, liver, and muscle functions, while choline deficiency is linked to disease states like fatty liver. Choline has important roles in neurodevelopment, cognition, liver function, lipid metabolism, and cardiovascular health. While its signaling role has been considered mostly indirect via acetylcholine and phosphatidylcholine which are synthesized from choline, emerging evidence supports a role for choline as an intracellular messenger acting on Sigma-1R, a non-opioid intracellular receptor. These new findings expand the cell signaling repertoire and increase the current understanding of the role of choline while warranting more research to uncover the molecular mechanisms and significance in the context of GPCR signaling, the relevance for physiology and disease states.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

40806292

Language

English

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