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.

Monounsaturated fatty acids (MUFA) are emerging health biomarkers, and in particular the ratio between palmitoleic acid (9cis-16:1) and palmitic acid (16:0) affords the delta-9 desaturase index that is increased in obesity. Recently, other positional and geometrical MUFA isomers belonging to the hexadecenoic family (C16 MUFA) were found in circulating lipids, such as sapienic acid (6cis-16:1), palmitelaidic acid (9trans-16:1) and 6trans-16:1. In this work we report: i) the identification of sapienic acid as component of human erythrocyte membrane phospholipids with significant increase in morbidly obese patients (n = 50) compared with age-matched lean controls (n = 50); and ii) the first comparison of erythrocyte membrane phospholipids (PL) and plasma cholesteryl esters (CE) in morbidly obese patients highlighting that some of their fatty acid levels have opposite trends: increases of both palmitic and sapienic acids with the decrease of linoleic acid (9cis,12cis-18:2, omega-6) in red blood cell (RBC) membrane PL were reversed in plasma CE, whereas the increase of palmitoleic acid was similar in both lipid species. Consequentially, desaturase enzymatic indexes gave different results, depending on the lipid class used for the fatty acid content. The fatty acid profile of morbidly obese subjects also showed significant increases of stearic acid (C18:0) and C20 omega-6, as well as decreases of oleic acid (9cis-18:1) and docosahexaenoic acid (C22:6 omega-3) as compared with lean healthy controls. Trans monounsaturated and polyunsaturated fatty acids were also measured and found significantly increased in both lipid classes of morbidly obese subjects. These results highlight the C16 MUFA isomers as emerging metabolic marker provided that the assignment of the double bond position and geometry is correctly performed, thus identifying the corresponding lipidomic pathway. Since RBC membrane PL and plasma CE have different fatty acid trends, caution must also be used in the choice of lipid species for the interpretation of lipidomic profiles.

The fatty acid (FA) composition of red blood cell (RBC) membrane phospholipids of cancer patients can reflect tumor status, dietary intakes, and cancer type or therapy. However, the characteristic membrane profiles have so far not yet defined as a potential biomarker to monitor disease evolution. The present work provides the first evidence of cancer metabolic signatures affecting cell membranes that are independent of nutritional habits. From the Oncology Outpatient Unit of the Onkologikoa hospital, two groups of cancer patients (n = 54) and healthy controls (n = 37) were recruited, and mature RBCs membrane phospholipids were analyzed for FA profiling (GC-MS). Dietary habits were evaluated using a validated food frequency questionnaire. The adjusted Analysis of Covariance Test (ANCOVA) model revealed cancer patients to have a lower relative percentage of saturated fatty acids (SFA) (C16:0 (5.7%); C18:0 (15.9%)), and higher monounsaturated fatty acids (MUFA) (9c-C18:1 (12.9%) and 11c-C18:1 (54.5%)), compared to controls. In line with this, we observe that the desaturase enzymatic index (delta-9 desaturase (Δ9D), +28.3%) and the membrane saturation index (SI = SFA/MUFA; −27.3%) were similarly modulated. Polyunsaturated fatty acids (PUFA) families showed an increase of n-6 C18:2 and C20:3 (15.7% and 22.2% respectively), with no differences in n-6 C20:4 and n-3 PUFA (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)). Importantly, these changes were found independent of foods and fat intakes from the diet. The membrane lipid profile in RBC was useful to ascertain the presence of two main metabolic signatures of increased desaturation activity and omega-6 in cancer patients, statistically independent from dietary habits.