# Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape
## 5 Lipidomic Insights of EAT  
As a derivative of metabolomics, lipidomics is considered an opportunity to approach EAT phenotypes from a biochemical perspective. More than genes and proteins, metabolites act as direct indicators of the physiological and pathological changes in the biochemical activity of EAT. An untargeted lipidomic study showed that EAT and SAT have completely different lipidomic profiles. For example, in comparison to SAT, the expression level of phosphatidylethanolamine in EAT was 20 times higher. Moreover, this molecule was the most important in discriminating patients with CAD from patients without. These data reflect a high number of cell membranes and emphasize the small nature of adipocytes in EAT compared to SAT [101]. High levels of phosphatidylethanolamine plasmalogens present in EAT suggest that these molecules could be involved in the regulation of mitochondrial dynamics, and therefore in the brown activation of EAT. Additionally, the lipidomic signature of EAT in CAD compared to non-CAD subjects presented more ceramides, diglycerides, and monoglycerides, and fewer unsaturated TGs [101]. Amongst these molecules, ceramides are of particular interest as they play a pivotal role in numerous inflammatory processes. Not only the total EAT ceramide level in CAD, but also the atherogenic ceramide ratios, report a strong association with the activity of an enzyme that could largely contribute to the EAT volume increase in CAD, lipoprotein lipase (LPL). This enzyme enhances the influx of free fatty acids from circulating TG-rich lipoproteins into EAT [102]. Ceramides have also been shown to lead to cellular dysfunction and apoptosis, a phenomenon referred to as lipotoxicity [103; 104]. Inflammation highlighted by transcriptomics and proteomics is considered a driver of the dyslipidemic phenotype associated with EAT, resulting in increased levels of triglycerides-rich lipoproteins that offer a protection by neutralizing inflammatory triggers [105]. Minor lipids could also have an important role in EAT metabolism. They can be detected by optimizing the preanalytical phase of lipid analysis in adipose tissue and separating triglycerides. This method allowed the identification of 37 lipid molecules that were under the limit of detection before because high molecular-mass molecules suppressed their ionization. EAT and SAT differed mainly in the following lipid classes: sphingomyelins, glycerophosphatidylcholines, glycerophosphatidyllinositols, and glycerophosphatidylethanolamine [106]. A more in-depth analysis identified differences in glycerolipids by means of saturation/unsaturation and the number of carbons of fatty acids present in these molecules. CAD was associated with high levels of saturated and monounsaturated fatty acids in TG. Meanwhile, in patients with both diabetes and CAD, these EAT levels were lower, especially for fatty acids with an odd number of carbons [107]. Interestingly, the plasma lipoprotein profile only partially reflects the EAT lipidome; therefore, circulating lipoproteins cannot be considered biomarkers for EAT lipid content [101; 107]. A relevant positive correlation was observed between dihydroxycholesterol in EAT and total plasma cholesterol in patients with diabetes and CAD, but not in patients with CAD and without diabetes [107]. Concerning the fact that high levels of oxysterols are associated with CAD, further lipidomic studies that include other molecules from the same class need to be performed on EAT in subjects with CAD to confirm or negate their direct role. Different diacylglycerollysperols present a significant but weak correlation with total cholesterol and HDL-cholesterol [107]. In patients with CAD, [PERSON] et al. attribute an EAT diacylglycerollyscerol (18:2/18:2) increase to the presence of type II diabetes [107], while [PERSON] et al. did not report distinct values in similar conditions [108].