## 1 Introduction: A New \"Omics\" Technology: Metabolomics  
Metabolomics (or metabonomics [1]) is used to define the large-scale study of small organic molecules, commonly known as metabolites (small molecules of 1 kilodalton, KDa), present within cells, biofluids, tissues or organisms. All of these small molecules taken together, and their interactions within a biological system, are known as the metabolome. This new discipline, together with the other omics techniques, helps reaching a complete view of cellular processes. The aim of this approach is to sketch, in cooperation with other omics technologies (genomics, transcriptomics and proteomics), a network of interactions that can describe, in detail, the state of the cell. This is called \"interactome analysis\" [2]. In fact, while genomics is the study of DNA and genetic information within a cell, transcriptomics is the study of RNA and differences in mRNA expression; proteomics is the large-scale study of proteins produced in an organism, system or biological context. In turn, metabolomics completes these studies, analyzing the substrates and products of metabolism as they are influenced by genetic and environmental factors (Figure 1). Metabolomics represents a powerful approach, because metabolites and their concentrations directly reflect the underlying biochemical activity and state of cells and/or tissues, producing the molecular phenotype. The set of these small molecules, such as peptides, amino acids, nucleic acids, carbohydrates, organic acids, vitamins, polyphenols and alkaloids, represents the metabolome, through which the final or intermediate products of a biochemical process can be studied in order to build a metabolic pathway [2]. This area of research produces a \"photo\" of a cell, which can help identify its current phase in the cell cycle, and help determine whether or not it is facing environmental stress or if it is correctly performing its physiological role [3]. In fact, metabolomics approaches are extensively used i. to evaluate responses to environmental stress; ii. to investigate toxicology, drug discovery [4] and nutrition [5]; iii. to study the global effects of genetic manipulation and cancer; iv. to discover natural products; and v. to compare different stages of growth [6; 7; 8; 9; 10; 11] (Figure 2). The concept of the metabolic profile first appeared in literature in the 1950s, but only in the following three decades was this area of research completely developed. Despite this observation, metabolomics has only recently aroused the interest of researchers, thanks to the development of advanced technologies for the quantification of metabolites, such as gas chromatography (GC) and mass spectrometry (MS) [3]. Initially, studies mainly concerned metabolites of specific compounds such as pharmaceutical products [12; 13]. Later, in this research area, studies on classes of compounds were included, such as catecholamines and oxylipins [14; 15; 16; 17]. In particular, quantitative determination of some metabolites of  
Figure 1: Four major “omics” fields, starting from genomics to metabolomics. Figure 2: The main applications of metabolomics and their relationships. catecholamines was performed with metabolomics approaches. These metabolites were used as biological markers for diagnosis, for evaluation of therapeutic responses, and for early recognition of tumor relapses derived from the neural crest (neuroblastoma, pheochromocytoma), carcinoid tumors and melanoma [14]. In addition, metabolomics approaches were used to identify oxygenated fatty acid derivatives, called oxylipins, mainly produced from diatoms. Oxylipins have a negative effect on reproduction and on the development of different marine invertebrates, such as copepods [18] and sea urchins [19], but these molecules also have a cytotoxic effect on several cancer cell lines [20]. Metabolomic research is primarily carried out in complex matrices such as blood, cells, plants or extracts of other marine organisms [21].