Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model.

World J Hepatol

Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Rio Grande do Sul, Brazil.

Published: December 2024

Background: Genetic and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis.

Aim: To evaluate micro (mi)RNAs and lipophagy markers in an experimental model of metabolic dysfunction-associated steatohepatitis (MASH).

Methods: Adult male Sprague Dawley rats were randomized into two groups: Control group ( = 10) fed a standard diet; and intervention group ( = 10) fed a high-fat-choline-deficient diet for 16 weeks. Molecular evaluation of lipophagy markers in liver tissue [sirtuin-1, p62/sequestosome-1, transcription factor-EB, perilipin-2 , , , lysosome-associated membrane proteins-2, rubicon, and ], and serum miRNAs were performed.

Results: Animals in the intervention group developed MASH and showed a significant decrease in sirtuin-1 ( = 0.020) and p62/sequestosome-1 ( < 0.001); the opposite was reported for transcription factor-EB ( = 0.020), ( = 0.003), ( = 0.031), and ( = 0.005) compared to the control group. There was no significant difference between groups for lysosome-associated membrane proteins-2 ( = 0.715), rubicon ( = 0.166), and ( = 0.312). The intervention group showed a significant increase in miR-34a ( = 0.005) and miR-21 ( = 0.043) compared to the control. There was no significant difference between groups for miR-375 ( = 0.905), miR-26b ( = 0.698), and miR-155 ( = 0.688).

Conclusion: Animals with MASH presented expression changes in markers related to lysosomal stress and autophagy as well as in miRNAs related to inflammation and fibrogenesis, processes that promote MASLD progression.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686535PMC
http://dx.doi.org/10.4254/wjh.v16.i12.1468DOI Listing

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