Mitochondrial dysfunction-related lipid changes occur in nonalcoholic fatty liver disease progression

Kang-Yu Peng, Matthew J. Watt, Sander Rensen, Jan Willem Greve, Kevin Huynh, Kaushala S. Jayawardana, Peter J. Meikle*, Ruth C. R. Meex*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Nonalcoholic fatty liver disease (NAFLD) comprises fat-accumulating conditions within hepatocytes that can cause severe liver damage and metabolic comorbidities. Studies suggest that mitochondrial dysfunction contributes to its development and progression and that the hepatic lipidome changes extensively in obesity and in NAFLD. To gain insight into the relationship between lipid metabolism and disease progression through different stages of NAFLD, we performed lipidomic analysis of plasma and liver biopsy samples from obese patients with nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) and from those without NAFLD. Congruent with earlier studies, hepatic lipid levels overall increased with NAFLD. Lipid species that differed with NAFLD severity were related to mitochondrial dysfunction; specifically, hepatic cardiolipin and ubiquinone accumulated in NAFL, and levels of acylcarnitine increased with NASH. We propose that increased levels of cardiolipin and ubiquinone may help to preserve mitochondrial function in early NAFLD, but that mitochondrial function eventually fails with progression to NASH, leading to increased acylcarnitine. We also found a negative association between hepatic odd-chain phosphatidylcholine and NAFLD, which may result from mitochondrial dysfunction-related impairment of branched-chain amino acid catabolism. Overall, these data suggest a close link between accumulation of specific hepatic lipid species, mitochondrial dysfunction, and the progression of NAFLD.

Original languageEnglish
Pages (from-to)1977-1986
Number of pages10
JournalJournal of Lipid Research
Volume59
Issue number10
DOIs
Publication statusPublished - Oct 2018

Keywords

  • lipidomics
  • liver metabolism
  • mitochondria
  • obesity
  • HEPATIC STEATOSIS
  • INSULIN SENSITIVITY
  • ELECTRON-TRANSPORT
  • OXIDATIVE STRESS
  • COMPLEX-I
  • RESPIRATORY-CHAIN
  • STEATOHEPATITIS
  • CARDIOLIPIN
  • ACIDS
  • METABOLISM

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