Lipidomics Revealed Aberrant Metabolism of Lipids Including FAHFAs in Renal Tissue in the Progression of Lupus Nephritis in a Murine Model.

Changfeng Hu,Qiao Duan,Xiaofen Xu,Zhijun Xie,Chengping Wen,Haichang Li,Xianlin Han,Yu Du

doi:10.3390/metabo11030142

Abstract

Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr mice in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the mice were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time.

Highlights

Systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease, is usually prevalent in women of child-bearing age and can affect the majority of the parts of the body, including the heart, skin, liver, blood vessel, and kidneys in particular [1]
The aberrant metabolism of the lipids contributes to the pathogenesis of Lupus nephritis (LN)
Numerous studies have demonstrated that there exists significant alteration of the lipid metabolism in the patients with SLE, including a “lupus pattern” of dyslipoproteinemia [3], aberrant chylomicron metabolism [4], enhanced lipid peroxidation [5,6], and other altered profiles of the lipids caused by increased oxidative stress, such as a marked reduction of ethanolamine plasmalogen species, and an obvious increase in the ethanolamine lysoglycerophospholipid and 4-hydroxyalkenals (4-HNE, the end products of lipid peroxidation) contents [7,8]

Summary

Introduction

Systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease, is usually prevalent in women of child-bearing age and can affect the majority of the parts of the body, including the heart, skin, liver, blood vessel, and kidneys in particular [1]. Accumulated evidence has supported the “lipid nephrotoxicity hypothesis” that lipid abnormalities could precipitate or/and aggravate glomerular and tubulointerstitial disease through interrupting lipid homeostasis of the renal tissue [9]. These events inevitably result in renal damage, contributing to the progression of LN, since lipids are essential constituents of the cellular membranes, maintaining the cellular functions

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Results

Conclusion