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

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.

Publication year:2021

Keywords:A1 Journal article

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BOF-publication weight:1

CSS-citation score:2

Authors:International

Authors from:Higher Education

Accessibility:Open