Abstract
Glucocorticoids (GCs) are commonly used to treat systemic lupus erythematosus (SLE). Unfortunately, excessive GCs can induce many side effects associated with disordered fatty acid (FA) metabolism. Although an increased level of total FA has been found after GCs treatment, it is not clear whether all FA species increased or only certain FA species were altered. A gas chromatography–mass spectrometry-based FA profiling approach was performed to reveal the alterations of FA species in SLE model mice (MRL/lpr) after treatment with 5 mg/kg of prednisone. The study showed a distinct FA profile in MRL/lpr mice compared to the controls, mainly manifested by elevated polyunsaturated FAs (arachidonate, docosahexaenoate, etc.), which are related to the inflammatory state; and altered (product FA/precursor FA) ratios representing the estimated activities of FA desaturase and elongase (higher activities of multiple elongases, △4 desaturase, △5 desaturase, △6 desaturase, and lower activity of △8 desaturase). Treatment with 5 mg/kg of prednisone decreased the total level of n-6 polyunsaturated FA in MRL/lpr mice; in particular, the level of arachidonate and estimated activity of △5 desaturase were reduced to the control level. Moreover, prednisone induced additional perturbations in FAs, including not only saturated FAs, but also monounsaturated FAs and n-3 polyunsaturated FAs, indicating that there was a strong effect of prednisone on FA metabolism. These results may be valuable for further studies of the side effects of GCs treatment.
Highlights
Systemic lupus erythematosus (SLE) is a typical, systemic autoimmune disease that causes damage to multiple organ systems (Lisnevskaia et al, 2014; Tsokos et al, 2016)
Thirty species of long chain Fatty acid (FA) were detected in the serum samples (Figure 2A), including ten saturated fatty acids (SFAs) (C12:0, C14:0, C15:0, C16:0, C17:0, C18:0, C19:0 C20:0, C22:0 and C24:0), eight monounsaturated fatty acids (MUFAs) (C16:1 n9, C16:1 n7, C17:1 n7, C18:1 n9, C18:1 n7, C20:1 n9, C22:1 n9, and C24:1 n9) and 12 polyunsaturated fatty acids (PUFAs) (C16:2 n6, C18:2 n6, C18:3 n3, C20:2 n6, C20:3 n6, C20:4 n6, C22:4 n6 iso, C20:5 n3, C22:4 n6, C22:5 n6, C22:5 n3, and C22:6 n3)
In order to generally observe the differences of FA profiles in all samples, principal component analysis (PCA) was performed based on the serum FAs data from the control, model and GC groups
Summary
Systemic lupus erythematosus (SLE) is a typical, systemic autoimmune disease that causes damage to multiple organ systems (Lisnevskaia et al, 2014; Tsokos et al, 2016). Epidemiological studies have shown that, compared with the general population, the prevalence of many metabolic disorders, such as abnormal glucose metabolism and disturbed lipid metabolism, has increased in patients with SLE (Tselios et al, 2016; Yan et al, 2016). Lipids are fundamental components of cells, and altered lipid metabolism can elevate the risk of cardiovascular disease and renal involvement in SLE patients (Frostegard et al, 2005; Teixeira and Tam, 2017). Fatty acid (FA) is an important kind of lipids with diverse functions, as part of cell membranes, and as energy sources that can participate in a wide range of physiological and pathological conditions (Falomir-Lockhart et al, 2019). According to the saturation degree of hydrocarbon chains, FAs can be divided into three types: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs)
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