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Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease

Abstract : Background: Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. The atypical class of deoxy-sphingolipids has been implicated in the metabolic syndrome and type 2 diabetes. Aim: To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. Methods: Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. Results: Two-hundred and eighty-eight patients were included. There was no association between typical sphingolipids and NAFLD and its different entities. There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. There was no association between these deoxy-sphingolipids and activity of the steatohepatitis, nor was there any association with fibrosis. Differences in deoxy-sphingolipids also correlated independently with the presence of the metabolic syndrome, but not diabetes. Conclusion: Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis.
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https://www.hal.inserm.fr/inserm-03180573
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Submitted on : Thursday, March 25, 2021 - 10:33:39 AM
Last modification on : Wednesday, November 3, 2021 - 2:56:06 PM
Long-term archiving on: : Saturday, June 26, 2021 - 6:26:03 PM

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J. Weyler, A. Verrijken, T. Hornemann, L. Vonghia, E. Dirinck, et al.. Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. Acta Diabetologica, Springer Verlag, 2020, 58 (3), pp.319-327. ⟨10.1007/s00592-020-01612-7⟩. ⟨inserm-03180573⟩

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