Abstract
Palmitic acid metabolism involves delta-9 and delta-6 desaturase enzymes forming palmitoleic acid (9cis-16:1; n-7 series) and sapienic acid (6cis-16:1; n-10 series), respectively. The corresponding biological consequences and lipidomic research on these positional monounsaturated fatty acid (MUFA) isomers are under development. Furthermore, sapienic acid can bring to the de novo synthesis of the n-10 polyunsaturated fatty acid (PUFA) sebaleic acid (5cis,8cis-18:2), but such transformations in cancer cells are not known. The model of Caco-2 cell line was used to monitor sapienic acid supplementation (150 and 300 μM) and provide evidence of the formation of n-10 fatty acids as well as their incorporation at levels of membrane phospholipids and triglycerides. Comparison with palmitoleic and palmitic acids evidenced that lipid remodelling was influenced by the type of fatty acid and positional isomer, with an increase of 8cis-18:1, n-10 PUFA and a decrease of saturated fats in case of sapienic acid. Cholesteryl esters were formed only in cases with sapienic acid. Sapienic acid was the less toxic among the tested fatty acids, showing the highest EC50s and inducing death only in 75% of cells at the highest concentration tested. Two-photon fluorescent microscopy with Laurdan as a fluorescent dye provided information on membrane fluidity, highlighting that sapienic acid increases the distribution of fluid regions, probably connected with the formation of 8cis-18:1 and the n-10 PUFA in cell lipidome. Our results bring evidence for MUFA positional isomers and de novo PUFA synthesis for developing lipidomic analysis and cancer research.
Highlights
The role of lipids in health is well known and lipidomics offers very powerful tools for the investigation of lipid involvement in disease onset and progress [1,2,3]
Caco-2 cells were treated with three fatty acid supplementations and the cell viability was evaluated at concentrations ranging from 100 to 300 μM (100, 150, 200, 250 and 300 μM) at different times up to 96 h, as shown in Figure 2A, expressing the percentage of viability compared to control cultures as mean ± SD of three different experiments
The highest toxic effect was reached for both fatty acids at 300 μM concentration, reducing cell viability almost to 0% for palmitoleic acid, whereas viability was not absent for sapienic acid, being reduced at 25% after 24 h and later
Summary
The role of lipids in health is well known and lipidomics offers very powerful tools for the investigation of lipid involvement in disease onset and progress [1,2,3]. Fatty acid-based membrane lipidomics and the corresponding molecular profiles provide insights of the naturally occurring and spontaneous process of lipid assembly combined with stabilized dietary intakes and biosynthesis [3]. Fatty acids are necessary building blocks for membrane phospholipid structures, regulating biophysical properties such as fluidity, dynamic features, and membrane protein functions, and have crucial importance for tumor development and disease progression [4,5]. Eukaryotic cells need polyunsaturated fatty acids (PUFA) to form their membranes; in cancer cells PUFAs exert various roles. Fatty acids accumulate as intracellular triglyceride depots, which are necessary both for cell energy and lipotoxicity control [8,9]
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