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

J Lipid Res 2018 10 24;59(10):1977-1986. Epub 2018 Jul 24.

Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands

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.

Download full-text PDF

Source
http://www.jlr.org/lookup/doi/10.1194/jlr.M085613
Publisher Site
http://dx.doi.org/10.1194/jlr.M085613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168306PMC
October 2018
12 Reads

Publication Analysis

Top Keywords

mitochondrial dysfunction
12
fatty liver
12
nonalcoholic fatty
12
nafld
9
liver disease
8
disease progression
8
mitochondrial function
8
hepatic lipid
8
lipid species
8
cardiolipin ubiquinone
8
mitochondrial dysfunction-related
8
mitochondrial
7
progression
5
hepatic
5
liver
5
lipid
5
studies hepatic
4
earlier studies
4
congruent earlier
4
phosphatidylcholine nafld
4

References

(Supplied by CrossRef)
Liver pathology in morbidly obese patients with and without diabetes
Silverman et al.
Am. J. Gastroenterol. 1990
Nonalcoholic fatty liver disease as a multi-systemic disease
Fotbolcu et al.
World J. Gastroenterol. 2016

Similar Publications