## 2 Omega-3 Polyunsaturated Fatty Acids
### Biological Functions  
The principal biological functions attributed to n-3 PUFAs encompass their pivotal roles as structural constituents within cellular membranes, providers of metabolic energy, and as regulatory agents orchestrating the modulation of intricate biochemical pathways through the generation of \"bioactive lipid\" molecules [28]. These multifaceted functionalities are integral to sustaining cellular integrity, facilitating energy homeostasis and governing a spectrum of physiological processes critical for our organism. In the context of cellular membranes, particularly within the vasculature, EPA assumes a notable role, exhibiting a stable conformation that contributes to the maintenance of cholesterol homeostasis and membrane fluidity. Conversely, within specialized neuronal and retinal tissues, DHA undergoes isomerization, thereby enhancing membrane fluidity and facilitating the sequestration of cholesterol into lipid rafts, characterized by an abundance of sphingolipids. Notably, a fraction of dietary ALA undergoes enzymatic conversion to EPA and DHA in adults, albeit with varying degrees of efficiency. Importantly, this conversion process is particularly augmented in women of reproductive age compared to men, attributable in part to the influence of plasma estrogen. However, notwithstanding endogenous enzymatic mechanisms, the primary source of EPA and DHA remains dietary intake, underscoring the imperative of dietary supplementation to meet optimal physiological requirements [29]. Other functions are related with intestinal immune tolerance and gut microbiota maintenance [30], pregnancy and lactation [27], cardiovascular health [31], cognitive function [32], skeletal muscle health [33], sarcopenia [34] and osteoarthritis [35], among others [18]. In the realm of inflammation regulation, PUFAs undergo enzymatic oxygenation, leading to the formation of oxylipins, a class of molecules integral to mediating inflammatory processes. Among these oxylipins, particular attention is directed towards pro-resolving mediators, encompassing resolvins, protecting and maresins, which function to expedite the resolution of inflammatory responses. Broadly, n-3 PUFAs serve as precursors for the synthesis of anti-inflammatory oxylipins, whereas n-6 PUFAs act as progenitors of pro-inflammatory mediators, thus influencing the initiation and termination phases of inflammation. Consequently, the balance between n-6 and n-3 PUFAs, reflected in the n-6/n-3 ratio, delineates a critical determinant of inflammatory modulation [36]. Furthermore, n-3 PUFAs exert regulatory effects on transcriptional processes, notably enhancing peroxisome proliferatorator-activated receptor alpha expression while concurrently attenuating the transcription of nuclear factor kappa B (NF-kB) and the NLR family pyrin domain containing (NLRP) 3 inflammasome, thereby exerting a suppressive influence on inflammatory cascades. Additionally, oxylipins are implicated in the modulation of ion channels, particularly within neuronal and muscular tissues, although the precise physiological implications of these interactions remain incompletely understood, warranting further investigation [37]. The n-3 PUFAs, in conjunction with their n-6 counterparts, serve as substrates contributing to the biosynthesis of compounds within the endocannabinoid system, comprising neurotransmitters, receptors and associated enzymes. These bioactive compounds exert far-reaching effects across various cerebral processes and peripheral tissues, prominently including the regulation of appetite. Notably, enzymatic metabolism of EPA and DHA culminates in the formation of N-eicosapentanoyl ethanolamine (EPEA) and N-docosahexaenoicenoyl ethanolamine (DHEA), both of which serve as endocannabinoids upon binding to their receptors, thereby orchestrating their biological functions [38]. EPEA and DHEA can be metabolized by cytochrome P450 to produce endocannabinoid epoxides, which have been shown to reduce inflammation and neoangiogenesis in animal models [39].