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Mol Nutr Food Res. 2018 Jul;62(13):e1800189. doi: 10.1002/mnfr.201800189. Epub 2018 Jun 12.

Impact of miR-140 Deficiency on Non-Alcoholic Fatty Liver Disease.

Author information

1
Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA.
2
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, 21202, USA.

Abstract

SCOPE:

We have previously shown that loss of miR-140 has a pro-fibrotic effect in the mammary gland. This study aims to investigate whether miR-140 loss and obesity act synergistically to promote non-alcoholic fatty liver disease (NAFLD), and to identify the underlying mechanisms.

METHODS AND RESULTS:

Liver tissues were isolated from lean-fat-diet and high-fat-diet fed wild-type and miR-140 knockout mice. Using molecular staining and immunohistochemistry techniques, increased development of NAFLD and fibrotic indicators in miR-140 knockout mice were identified. Utilizing an in vitro model system, miR-140 was demonstrated to target TLR-4, and miR-140 overexpression was shown to be sufficient to inhibit palmitic acid signaling through the TLR-4/NFκB pathway.

CONCLUSION:

These findings demonstrate that loss of miR-140 results in increased expression of TLR-4, sensitizing cells to palmitic acid signaling and in increased inflammatory activity through the TLR4/NFκB pathway. This signaling axis promotes NAFLD development in a high-fat diet context and indicates the potential utility of miR-140 rescue as a therapeutic strategy in NAFLD.

KEYWORDS:

TLR-4; miR-140; non-alcoholic fatty liver disease (NAFLD); obesity; palmitic acid

PMID:
29701903
PMCID:
PMC6280970
DOI:
10.1002/mnfr.201800189
[Indexed for MEDLINE]
Free PMC Article

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