**1. Introduction**

Polyunsaturated fatty acid (PUFA) imbalance is linked with various clinical conditions, especially neuropsychiatric diseases, including schizophrenia [1]. Numerous reports confirmed that patients

with schizophrenia (SZ) have lower levels of blood omega-3 fatty acids (FAs) compared with healthy individuals [2,3]. The comparison of the erythrocyte FA composition in 429 subjects with schizophrenia and 444 healthy individuals revealed that the patients had lower levels of omega-3 PUFAs fatty acids: docosahexaenoic acid (DHA, 22:6), docosapentaenoic acid (DPA, 22:5), eicosapentaenoic acid (EPA, 20:5), and an omega-6 fatty acid, arachidonic acid (AA, 20:4) [4]. The mechanism of undernutrition of PUFAs in the SZ population is still under examination. Studies indicated that several factors engage in improper FA blood concentrations, including poor nutrition, antipsychotic drug interactions with cell membranes, and disturbances of lipid metabolism, as well as fatty acid-dependent signaling pathways [2,3,5].

The clinical findings support the abnormal metabolism of FAs in SZ, reflected by attenuation of responses to the niacin skin flush test. The dermal application of aqueous methyl nicotinate (AMN) leads to redness, as well as edema of skin as a result of the cascade of inflammatory reactions mediated by phospholipase A2 (PLA2) [6,7]. PLA2 activates the release of omega-6 AA from membrane phospholipids which is related to various physiological processes connected with emotions, motivation, response to stress, and energy homeostasis, including eicosanoid biosynthetic enzymes, as well as promotion of the immune type 2 response and initiation of endocannabinoid signaling in the brain [8,9].

PLA2 activity can be modulated by a G-coupled receptor responsive to fatty acids—GPR120 (also known as an free fatty acid receptor 4: FFAR4). Omega-3 PUFAs are endogenous ligands of the receptor. FA stimulation leads to GPR120–β-arrestin-2 complex formation and contributes to anti-inflammatory signaling pathway activation [10]. GPR120 is a therapeutic target in many diseases, especially diabetes and other inflammatory conditions [11]. Taking into account lipid disturbances in schizophrenia and the mechanistic and genetic connection between schizophrenia and inflammatory disorders, GPR120 could also be a promising target in this condition [12]. An animal study showed that receptor activation in the microglia of the hypothalamus reduces neuroinflammation via a decrease in pro-inflammatory cytokine synthesis [13]. However, little is known about GPR120 in psychiatric disorders. To our best knowledge, no clinical studies are concerned about the role GPR120 signaling together with FA metabolism in schizophrenia.

**The aim** of the study was to determine the differences in PUFAs nutritional status and metabolism between patients with schizophrenia and healthy individuals. More specifically, we examined and compared serum concentrations of GPR120, polyunsaturated fatty acids (omega-6: AA, omega-3: DHA, EPA, α-linolenic acid (ALA)) and dietary intake of omega-3 and omega-6 FAs (omega-6: LA—linolenic acid (precursor of AA)), omega-3: DHA, EPA, ALA) between patients and healthy individuals. The secondary aim was to find a relationship between PUFA metabolism and clinical/sociodemographic variables in the examined population.
