Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease

Yanyong Xu, Yingdong Zhu, Shuwei Hu, Xiaoli Pan, Fathima Cassim Bawa, Helen H. Wang, David Q.H. Wang, Liya Yin, Yanqiao Zhang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objective: Hepatic miR-34a expression is elevated in diet-induced or genetically obese mice and patients with non-alcoholic steatohepatitis (NASH), yet hepatocyte miR-34a's role in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to NASH remains to be elucidated. Methods: Mice overexpressing or deficient in hepatocyte miR-34a and control mice were fed a diet enriched in fats, cholesterol, and fructose (HFCF) to induce NASH. C57BL/6 mice with NASH were treated with an miR-34a inhibitor or a scramble control oligo. The effect of miR-34a on the development, progression, and reversal of NAFLD was determined. Results: The hepatocyte-specific expression of miR-34a aggravated HFCF diet-induced NAFLD. In contrast, germline or adult-onset deletion of hepatocyte miR-34a attenuated the development and progression of NAFLD. In addition, pharmacological inhibition of miR-34a reversed HFCF diet-induced steatohepatitis. Mechanistically, hepatocyte miR-34a regulated the development and progression of NAFLD by inducing lipid absorption, lipogenesis, inflammation, and apoptosis but inhibiting fatty acid oxidation. Conclusions: Hepatocyte miR-34a is an important regulator in the development and progression of NAFLD. MiR-34a may be a useful target for treating NAFLD.

Original languageEnglish (US)
Article number101244
JournalMolecular Metabolism
Volume51
DOIs
StatePublished - Sep 2021

Keywords

  • Bile acids
  • Lipid absorption
  • Lipogenesis
  • NAFLD
  • miR-34a

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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