Abstract
Although the conjugated linoleic acids (CLA) have several isomer-specific biological effects including anti-carcinogenic and anti-adipogenic effects, their mechanisms of action remain unclear. To determine their potential effects on membrane structure and function, we studied the incorporation profiles of four CLA isomers ( trans-10 cis-12 (A), trans-9 trans-11 (B), cis-9 trans-11 (C), and cis-9 cis-11 (D)) in CHO and HepG2 cells. All four isomers were incorporated into cellular lipids as efficiently as linoleic acid (LA), with the majority of the incorporated CLA present in membrane rafts. Of the four isomers, only CLA-A increased the cholesterol content of the raft fraction. Over 50% of the incorporated CLAs were recovered in phosphatidylcholine of CHO cells, but in HepG2 the neutral lipids contained the majority of CLA. The desaturation index (18:1/18:0 and 16:1/16:0) was reduced by CLA-A, but increased by CLA-B, the effects being apparent mostly in raft lipids. The Δ 9 desaturase activity was inhibited by CLAs A and C. Unlike LA, which was mostly found in the sn-2 position of phospholipids, most CLAs were also incorporated significantly into the sn-1 position in both cell types. These studies show that the incorporation profiles of CLA isomers differ significantly from that of LA, and this could lead to alterations in membrane function, especially in the raft-associated proteins.
Highlights
Conjugated linoleic acids (CLA), the naturally occurring isomers of linoleic acid (LA), have been reported to have several beneficial effects including anti-carcinogenic, antiinflammatory, and anti-obesity effects [1,2,3], but the underlying mechanisms are poorly understood
The present studies show that all CLA isomers are incorporated efficiently into cell membranes, and metabolized comparably to the unconjugated LA
They further show that more than 50% of CLA was present in the raft domains of the membranes, in contrast to the omega-3 fatty acids which tend to excluded from the raft domains [26]
Summary
Conjugated linoleic acids (CLA), the naturally occurring isomers of linoleic acid (LA), have been reported to have several beneficial effects including anti-carcinogenic, antiinflammatory, and anti-obesity effects [1,2,3], but the underlying mechanisms are poorly understood. The possible effects of CLA isomers on membrane structure and function have not been investigated, and no systematic studies on their incorporation profiles, especially in the raft and non-raft lipids, have been carried out. The CLAs replaced 18:1 in most cases, inhibited the Δ9 desaturase activity in an isomer-specific manner, and unlike the unconjugated 18:2 (LA), were incorporated significantly into the sn-1 position of phospholipids. These results support the hypothesis that CLA may exert part of their biological effects through modification of membrane lipid composition and function, especially in the raft domains
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Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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