HDL biology
Free fatty acids fluidize the lipoprotein surface, offering a physical explanation for how they modulate CETP activity (Eur J Biochem 1996)
Original title: Alterations of lipoprotein fluidity by non-esterified fatty acids known to affect cholesteryl ester transfer protein activity. An electron spin resonance study
Using electron spin resonance (ESR) with spin-labeled stearic acid, this study measured how saturated, monounsaturated, and polyunsaturated non-esterified fatty acids (NEFA) alter lipoprotein surface fluidity, since NEFA are known to affect CETP activity. In non-enriched lipoproteins, HDL3 had a more ordered surface than LDL, but incubating either particle with NEFA significantly increased fluidity, with the effect depending on the NEFA acyl chain: medium-chain fatty acids (lauric and myristic) fluidized more than shorter or longer saturated homologues, and introducing a double bond further increased fluidizing ability compared with saturated NEFA of the same length. The magnitude of fluidity change in both LDL and HDL3 depended on the final NEFA to lipoprotein ratio. The authors conclude that the ability of NEFA to modulate CETP activity may relate in part to these NEFA-induced alterations in lipoprotein surface fluidity.
Original abstract
The aim of the present study was to investigate the effect of saturated, monounsaturated and polyunsaturated non-esterified fatty acids (NEFA) on lipoprotein fluidity by using the electron spin resonance (ESR) method. The fluidity of the lipid phase of lipoproteins was evaluated by calculating from ESR spectra the S parameter of three different positional isomers of spin-labeled stearic acid incorporated into the lipoprotein. In non-enriched lipoproteins, S values were higher in high-density lipoprotein 3 (HDL3) than in low-density lipoprotein (LDL) indicating that the surface of HDL3 was more ordered. Prior incubation of lipoprotein particles with NEFA significantly reduced S values, indicating an increased lipoprotein fluidity as compared with non-supplemented homologous samples. In NEFA-enriched lipoproteins, the modifications in fluidity were shown to be dependent on the structure of the NEFA acyl carbon chains. Medium-chain fatty acids [lauric (12:0) and myristic (14:0) acids] appeared to be better fluidizing molecules as compared with both shorter [octanoic (8:0) and decanoic (10:0) acids] and longer [palmitic (16:0) and stearic (18:0) acids] homologues. In addition, introducing at least one double bond in the acyl carbon chain significantly increased the ability of NEFA to reduce S as compared with saturated homologues. In both LDL and HDL3, the extent of the modifications of the molecular mobility at the lipoprotein surface was dependent on the final NEFA/lipoprotein ratio. In conclusion, these results suggest that the ability of NEFA to modulate the activity of the cholesteryl ester transfer protein might relate in part to alterations in fluidity at the lipoprotein surface.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.