Ethnicity-specific alterations of plasma and hepatic lipidomic profiles are related to high NAFLD rate and severity in Hispanic Americans, a pilot study

Authors: MAZI, TAGREED - University Of California, Davis; BORKOWSKI, KAMIL - University Of California, Davis; Newman, John; FIEHN, OLIVER - University Of California, Davis; BOWLUS, CHRISTINE - University Of California, Davis; SRKAR, SOUVIK - University Of California, Davis; MATSUKUMA, KAREN - University Of California, Davis; ALI, MOHAMED - University Of California, Davis; KIEFFER, DOROTHY - University Of California, Davis; WAN, YU-JUI - University Of California, Davis; STANHOPE, KIMBER - University Of California, Davis; HAVEL, PETER - University Of California, Davis; MEDICI, VALENTINA - University Of California, Davis

Submitted to: Free Radical Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2021
Publication Date: 4/10/2021
Citation: Mazi, T.A., Borkowski, K., Newman, J.W., Fiehn, O., Bowlus, C., Srkar, S., Matsukuma, K., Ali, M.R., Kieffer, D.A., Wan, Y.Y., Stanhope, K.L., Havel, P.J., Medici, V. 2021. Ethnicity-specific alterations of plasma and hepatic lipidomic profiles are related to high NAFLD rate and severity in Hispanic Americans, a pilot study. Free Radical Biology and Medicine. https://doi.org/10.1101/2021.04.08.21254907.
DOI: https://doi.org/10.1101/2021.04.08.21254907

Interpretive Summary: The objective of this study was to investigate metabolomic profiles in a group of Hispanic (HIS) and White Caucasian (CAU) with obesity and biopsy-confirmed NAFLD. The identification of metabolomic differences between HIS and CAU subjects with NAFLD may provide a new research direction pointing towards ethnicity-specific changes as potential drivers for the disparity observed in NAFLD rate and progression. To this end, we employed untargeted metabolomic profiling of primary metabolism, complex lipids, choline and related metabolites in a group of Hispanic (NAFL-HIS) and Caucasian (NAFL-CAU) subjects with obesity and NAFLD of comparable histological presentations, as compared to a group of ethnicity-matched lean healthy control subjects. The findings provide preliminary evidence that ethnicity-related variations in lipid metabolism may underlay the increased NAFLD risk and progression rate in those of Hispanic descent.

Technical Abstract: Nonalcoholic fatty liver disease (NAFLD) is a progressive condition that includes steatosis (NAFL) and nonalcoholic steatohepatitis (NASH). Hispanics (HIS) are afflicted with NAFLD at a higher rate and severity compared to other ethnicities. To date, the mechanisms underlying this disparity remain unelucidated. In this pilot study, we compared untargeted plasma metabolomic profiles for primary metabolism, complex lipids, choline and related compounds between a group of HIS (n =7) and White Caucasian (CAU, n =8) subjects with obesity and biopsy-characterized NAFL to ethnicity-matched lean healthy controls (n =14 HIS and 8 CAU). We also compared liver and plasma profiles in a group of HIS and CAU subjects with obesity and NASH of comparable NAFLD Activity Scores, to BMI-matched NASH-free subjects in both ethnicities. Results highlight signs of metabolic dysregulations observed in HIS, independent of obesity, including higher plasma triglycerides, acylcarnitines, and free fatty acids. With NASH progression, there were ethnicity-related differences in the hepatic profile, including higher free fatty acids and lysophospholipids seen in HIS, suggesting lipotoxicity involved in NASH progression. We also observed higher hepatic and plasma triglycerides, lower hepatic phospholipids with signs of impaired hepatic mitochondrial ß-oxidation. These findings provide preliminary evidence indicating ethnicity-related variations possibly modulating NAFLD risk and progression rate.