The influence of sex and gonadectomy on hepatic and brain fatty acid composition, lipogenesis and β‐oxidation

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Fatty acids are important molecules in living organisms, serving as an energy substrate, as the structural components of cell membranes, ligands for transcriptional factors involved in gene expression and as precursors of lipid mediators such as eicosanoids, resolvins and neuroprotectins (Kremmyda et al., 2011; Tvrzicka et al., 2011; Jump et al., 2013). Metabolic diseases, such as diabetes, obesity or metabolic syndrome, as well as several other diseases such as hypertension, coronary heart disease, alcoholism, schizophrenia, depression, Alzheimer's disease, atherosclerosis and cancer, are characterized by disturbances in fatty acid metabolism. The progression of these diseases could be, at least partially, influenced by fatty acid supplementation (Mocellin et al., 2016; Mašek et al., 2014; Ito, 2015; Wani et al., 2015; Endo and Arita, 2016; Pawełczyk et al., 2016). Consequently, fatty acid metabolism is being extensively investigated due to its significant clinical implications (Yashodhara et al., 2009).
De novo lipogenesis and bioconversion of long‐chain polyunsaturated fatty acids (LCPUFA) are regulated by desaturation and elongation enzymes, competition for these rate‐limiting enzymes between the n3 and n6 lines, partitioning into oxidation, esterification into phospholipids, different metabolites, substrate availability from food, transcriptional factors, hormones and microRNA (Wang et al., 2006; Childs et al., 2010; Tu et al., 2010; Fernández‐Hernando et al., 2011; Jump et al., 2013).
Testosterone and oestrogens have an important role in carbohydrate, protein and fat metabolism. Sex hormones influence the fatty acid composition and expression of genes involved in lipid metabolism. Nevertheless, molecular mechanisms have still not been completely elucidated (Kelly and Jones, 2013; Shen and Shi, 2015). Ovariectomy and orchidectomy are still important experimental models for the study of sex hormone deficiency and its influence on fatty acid metabolism (Perez et al., 2009; Alessandri et al., 2011; Kitson et al., 2013). These investigations are becoming even more interesting in the light of the recent dramatic increase in the incidence of metabolic syndrome and diabetes mellitus, and the recently discovered connection between these diseases and sex hormones and their receptors (Chow et al., 2011; Høst et al., 2013; Zhang et al., 2013; Cai et al., 2015).
The aim of this study was to determine, using a rat model, the relationship between sex hormones and tissue fatty acid composition. In addition, we investigated the effects of sex and gonadectomy on the expression of key genes involved in lipogenesis and mitochondrial and peroxisomal β‐oxidation. The results of this study will help to explain whether sex should be regarded as a significant variable in scientific studies investigating fatty acid composition, lipogenesis and β‐oxidation, and whether the differences are equally significant in both sexes.
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