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

  • Author(s): Mazi, Tagreed;
  • Borkowski, Kamil;
  • Newman, John;
  • Fiehn, Oliver;
  • Bowlus, Christopher;
  • Sarkar, Souvik;
  • Matsukuma, Karen;
  • Ali, Mohamed;
  • Kieffer, Dorothy;
  • Wan, Yu-Jui;
  • Stanhope, Kimber;
  • Havel, Peter;
  • Medici, Valentina
  • et al.

Published Web Location

https://www.medrxiv.org/content/10.1101/2021.04.08.21254907v1.full-text
No data is associated with this publication.
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a progressive condition that includes steatosis (NAFL) and nonalcoholic steatohepatitis (NASH). In the U.S., Hispanics (HIS) are afflicted with NAFLD at a higher rate and severity compared to other ethnicities. To date, the mechanisms underlying this disparity have not been elucidated. 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 metabolomic 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 dysregulation 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 is involved in the progression of NASH. We also observed greater hepatic triglyceride content, higher plasma triglyceride concentrations and lower hepatic phospholipids with signs of impaired hepatic mitochondrial β-oxidation. These findings provide preliminary evidence indicating ethnicity-related variations that could potentially modulate the risk for progression of NALD to NASH.

Highlights

Hispanic subjects show signs of metabolic dysregulations independent of obesity. In nonalcoholic fatty liver, plasma metabolomic profiles are differentially altered between ethnicities. In nonalcoholic steatohepatitis, the hepatic lipidomic profiles are differentially altered between ethnicities. In Hispanics, nonalcoholic steatohepatitis shows higher triglycerides and lipotoxic lipids with signs of impaired hepatic mitochondrial β-oxidation. Our results indicate evidence of ethnicity-related variations in the pathogenesis of nonalcoholic fatty liver disease.

Graphical Abstract

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