Fatty acid-related modulations of membrane fluidity in cells: detection and implications

Abstract

Metabolic homeostasis of fatty acids is complex and well-regulated in all organisms. The biosynthesis of saturated fatty acids (SFA) in mammals provides substrates for β-oxidation and ATP production. Monounsaturated fatty acids (MUFA) are products of desaturases that introduce a methylene group in cis geometry in SFA. Polyunsaturated fatty acids (n-6 and n-3 PUFA) are products of elongation and desaturation of the essential linoleic acid and α-linolenic acid, respectively. The liver processes dietary fatty acids and exports them in lipoproteins for distribution and storage in peripheral tissues. The three types of fatty acids are integrated in membrane phospholipids and determine their biophysical properties and functions. This study was aimed at investigating effects of fatty acids on membrane biophysical properties under varying nutritional and pathological conditions, by integrating lipidomic analysis of membrane phospholipids with functional two-photon microscopy (fTPM) of cellular membranes. This approach was applied to two case studies: first, pancreatic beta-cells, to investigate hormetic and detrimental effects of lipids. Second, red blood cells extracted from a genetic mouse model defective in lipoproteins, to understand the role of lipids in hepatic diseases and metabolic syndrome and their effect on circulating cells.

Keywords:

• Membrane fluidity
• functional two photon microscopy
• lipidomic analysis
• saturated fatty acids
• lipoproteins

Acknowledgements

GM would like to acknowledge Mario Amici and Daniela Samengo for their excellent technical assistance and the support by Fondi di Ateneo, UCSC Rome, Italy (Linea D1 to GM, GP and MDS). The confocal analysis has been performed at Labcemi, UCSC, Rome. SS is Adolf D. and Horty Storch Chair in Pharmaceutical Sciences, at the Faculty of Medicine, The Hebrew University of Jerusalem, Israel. He is affiliated with the David R. Bloom Center for Pharmacy and the Dr. Adolf and Klara Brettler Center for Research of Molecular Pharmacology and Therapeutics in the Hebrew University. KK is the chairman of the Pharmacology Department of the University of Patras Medical School and the director of the University of Patras research network “MetSNet”. The authors acknowledge the contribution of Lipinutragen srl in providing membrane lipidomic methodologies and information from its human lipidome database.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

All authors gratefully acknowledge the support and networking opportunities they received and enjoyed from COST (European Cooperation in Science and Technology) Action CM1201 on “Biomimetic Radical Chemistry”. This COST Action also provided Short-Term Scientific Mission (STSM) fellowships to BD and PP for training in confocal microscopy at GM Laboratory in Rome and for GM training in beta cell research at the laboratory in Jerusalem. SS would like to acknowledge support from Legacy Heritage Biomedical Science Partnership of the Israel Science Foundation of the Israel Academy of Sciences and Humanities (1429/13), the Vigevani Foundation, the Brettler Center for Research of Molecular Pharmacology and Therapeutics in the Hebrew University. GM would like to acknowledge Università Cattolica del Sacro Cuore, 10.13039/501100005743 [D1 2015]. KK would like to acknowledge the support of RioPharm Pharmaceuticals (Patras, Greece) the action “Supporting post-doctoral researchers” of the Operational Program “Education and Lifelong Learning” of the Greek General Secretariat of Research and Technology (grant LS4-858) and the action Siemens Excellence award with the acronym “EC3HDLglucose” financed by the Hellenic State Scholarships Foundation (IKY).