Differential effects of conjugated linoleic acid isomers on the biophysical and biochemical properties of model membranes

Abstract

Conjugated linoleic acids (CLA) are known to exert several isomer-specific biological effects, but their mechanisms of action are unclear. In order to determine whether the physicochemical effects of CLA on membranes play a role in their isomer-specific effects, we synthesized phosphatidylcholines (PCs) with 16:0 at sn-1 position and one of four CLA isomers (trans10 cis12 (A), trans9 trans11 (B), cis9 trans11 (C), and cis9 cis11 (D)) at sn-2, and determined their biophysical properties in monolayers and bilayers. The surface areas of the PCs with the two natural CLA (A and C) were similar at all pressures, but they differed significantly in presence of cholesterol, with PC-A condensing more than PC-C. Liposomes of PC-A similarly showed increased binding of cholesterol compared to PC-C liposomes. PC-A liposomes were less permeable to carboxyfluorescein compared to PC-C liposomes. The PC with two trans double bonds (B) showed the highest affinity to cholesterol and lowest permeability. The two natural CLA PCs (A and C) stimulated lecithin-cholesterol acyltransferase activity by 2-fold, whereas the unnatural CLA PCs (B and D) were inhibitory. These results suggest that the differences in the biophysical properties of CLA isomers A and C may partly contribute to the known differences in their biological effects.

Enhancement of antibody synthesis in rats by feeding cis-9,trans-11 conjugated linoleic acid during early life

“…But this is not the case for the 3-week group due to the time lapse between the last CLA intake and the day of quantification of CLA plasma content. The CLA membrane incorporation suggested here agrees with the study of Subbaiah et al [39], which demonstrates that CLA is incorporated into cell membranes to varying extent, depending upon the experimental conditions.…”

Molecular dynamic simulation study of cholesterol and conjugated double bonds in lipid bilayers

“…[33] Monolayer isotherms, at a temperature of 24 °C and a pressure of 15 mN/m, yield areas per molecule for both CLA isomers, with Chol concentrations of 0%, 10%, and 30%, that are comparable to the simulated areas in Figure 2. Figure 3 shows experimental isotherms (3a), molecular areas at 15 mN/m (3b), and Chol-induced condensation at 15 mN/m (3c).…”

“…Figure 3 shows experimental isotherms (3a), molecular areas at 15 mN/m (3b), and Chol-induced condensation at 15 mN/m (3c). Condensation percentages in the monolayer experiments are calculated as described in [33], and utilize experimental areas for pure CLA and for pure Chol monolayers. Since pure Chol molecular areas are not available for the simulations, we simply compare differences in condensation percentages for each isomer at each Chol concentration with the simulation prediction that those should be very small for each isomer.…”

Chemical and physiological aspects of isomers of conjugated fatty acids

“…More recently, CLAs have shown to undergo elongation and desaturation processes similar to those that occur with linoleic acid. This suggests that the CLAs mechanisms of action may be directly related to their properties and metabolism as unsaturated fatty acids (CZAUDERNA; KOWALCZYK; KORNILUK, 2007;SUBBAIAH et al, 2010).…”

“…In adipose and mammary tissues, the metabolite content ranges from 5 to 15% of total CLAs and in plasma and liver from 10 to 30% (BANNI, 2002). CLAs, like other PUFAs, have been shown to be incorporated into membrane lipids with the extent of incorporation ranging from <1 to >50% of total phospholipid fatty acids in various cells (SUBBAIAH et al, 2010).…”