Lipid crystallization

Lipid crystallization refers to the physicochemical process where lipid molecules, particularly cholesterol, transition from a disordered fluid state into a highly ordered solid crystalline lattice (PNAS, 2024 [1]; PubMed, 2012 [23]). While it is a fundamental property of lipids in various environments, in human pathology, it serves as a key driver of atherosclerosis, gallstone disease, and metabolic dysfunction-associated steatohepatitis (MASH) (PNAS, 2024 [1]; MDPI, 2022 [2]). Within arterial walls or hepatic tissues, these crystals act as mechanical stressors and endogenous danger signals that activate the NLRP3 inflammasome, triggering the release of pro-inflammatory cytokines such as IL-1 beta and promoting tissue stiffening (PNAS, 2024 [1]; Nature, 2010). Pharmacological strategies focus on preventing nucleation by lowering lipid levels using statins or ezetimibe, or actively dissolving existing crystals using agents like 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) (Patsnap, 2025 [14]; PMC, 2022 [6]). Targeting the inhibition of lipid crystallization is considered a promising approach to addressing residual inflammatory risk in patients with metabolic and cardiovascular disorders (PNAS, 2024 [1]).

Other names

Cholesterol crystallizationLipid solidificationLipid crystal formationCholesterol crystal nucleation

Dissolution of pre-existing lipid crystals via molecular sequestration or reduction of lipid concentrations to prevent reaching the saturation point required for crystal nucleation.