Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics

Abstract

Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress-with an excess of radical and oxidative processes-cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i) monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1); and (ii) the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects.

Keywords: fatty acid balance; gas chromatographic resolution; geometrical and positional isomers; membrane fatty acid biomarker; membrane lipidomics; palmitoleic acid; red blood cell membrane; sapienic acid.

Figure 1

Main lipid classes present in blood: triglyceride (A); cholesterol (B); phospholipid as phosphatidyl choline (C); cholesteryl ester (D) shown as representative chemical structures and molecular models, showing the oxygen atoms in red and the hydrogen atoms in white, whereas the carbon atoms in the structures are in black or in other colors.

Figure 2

Major biosynthetic pathways of polyunsaturated fatty acids (ω-3 and ω-6) with the interplay of desaturation (Δ5, Δ6) providing double bonds in cis geometric configuration (vertical arrows). The elongation step adds a two carbon atom-unit to the fatty acid chain (CE, chain elonagtion). * beta-oxidation. DGLA: Dihomo-γ-linolenic acid; DHA: Docosahexaenoic acid; EPA: Eicosapentaenoic acid.

Figure 3

Positional isomers of hexadecenoic fatty acids with the carbonyl group in position 1 and the double bond in different positions along the chian numbered in red: in C6–C7 (1); C7–C8 (2) and C9–C10 (3). Each of these molecules can exist also as a geometrical trans isomer (4, 5 and 6, respectively).

Figure 4

Gas chromatography (GC) elution window and mass spectra of the three dimethyl disulfide (DMDS) derivatives obtained from delta-6 (A); delta-7 (B) and delta-9 (C) with diagnostic mass fragments (ω-fragment and Δ-fragment) in colored boxes as well as in the panel D (see supplementary data of [14] for further details).

Figure 5

RBC membrane fatty acid families and types of human subjects of different ages in healthy (CTR) and pathological conditions (panels A–E); (A) morbid obesity [22]; (B) autism [44]; (C) colorectal cancer [49]; (D) iron deficient anemia [50]; (E) mild cognitive impairment [51]; panel (F) reports the RBC membrane status before and after an omega-3 supplementation of 3 months carried out in infertile men [45].