Plasma oxylipin profile discriminates ethnicities in subjects with Non-alcoholic steatohepatitis: An exploratory analysis

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver pathologies from steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). With no clear mechanism, it affects Hispanics in the U.S. disproportionately compared to other ethnicities. Polyunsaturated fatty acids (PUFAs) metabolism and downstream inflammatory lipid mediators including oxylipin (OXL) and endocannabinoid (eCB) are altered in NAFLD and thought to contribute to its pathogenesis. It is not clear if variations in PUFA metabolism and downstream lipid mediators characterize ethnicity in NAFLD. This pilot study employed targeted lipidomic profiling for plasma PUFAs, non-esterified OXLs and eCBs in White Hispanics (HIS, n =10) and Caucasians (CAU, n =8) with obesity and biopsy-confirmed NAFL, compared with healthy control subjects (HC; n =14 HIS; n =8 CAU). Results indicate diminished long chain PUFA profile in HIS with NAFL and NASH, independent of obesity and histological severity. The profiling data also detected differences in plasma OXLs and eCBs profiles by ethnicity group in NASH, including lower levels of arachidonic acid derived OXLs observed in HIS. We conducted a secondary analysis to compare ethnicities within NASH (n =12 HIS; n =17 CAU). Results showed that plasma OXL profiles distinguished ethnicities with NASH and confirmed ethnicity-related differences in arachidonic acid metabolism. Our data also suggest lower lipoxygenase(s) and higher soluble epoxide hydrolase(s) activities in HIS compared to CAU with NASH. The underlying causes and implications of these differences on NAFLD severity are not clear and worth further investigation. Our findings provide preliminary data suggesting ethnicity-specific plasma lipidomic signature characterizing NASH that requires validation.