10.6084/M9.FIGSHARE.18586089.V1
Yuanjie Yu
Yuanjie
Yu
Tian Tian
Tian
Tian
Shiyun Tan
Shiyun
Tan
Pengbo Wu
Pengbo
Wu
Yitian Guo
Yitian
Guo
Ming Li
Ming
Li
Mengjun Huang
Mengjun
Huang
MicroRNA-665-3p exacerbates nonalcoholic fatty liver disease in mice
<p>Oxidative stress and chronic inflammation are major culprits of nonalcoholic fatty liver disease (NAFLD). MicroRNA-665-3p (miR-665-3p) is implicated in regulating inflammation and oxidative stress; however, its role and molecular basis in NAFLD remain elusive. Herein, we measured a significant upregulation of miR-665-3p level in the liver and primary hepatocytes upon high fat diet (HFD) or 0.5 mmol/L palmitic acid plus 1.0 mmol/L oleic acid stimulation, and the elevated miR-665-3p expression aggravated oxidative stress, inflammation and NAFLD progression in mice. In contrast, miR-665-3p inhibition by the miR-665-3p antagomir significantly prevented HFD-induced oxidative stress, inflammation and hepatic dysfunction in vivo. Manipulation of miR-665-3p in primary hepatocytes also caused similar phenotypic alterations in vitro. Mechanistically, we demonstrated that miR-665-3p directly bound to the 3ʹ-untranslated region of fibronectin type III domain-containing 5 (FNDC5) to downregulate its expression and inactivated the downstream AMP-activated protein kinase alpha (AMPKα) pathway, thereby facilitating oxidative stress, inflammation and NAFLD progression. Our findings identify miR-665-3p as an endogenous positive regulator of NAFLD via inactivating FNDC5/AMPKα pathway, and inhibiting miR-665-3p may provide novel therapeutic strategies to treat NAFLD.</p>
Biochemistry
Microbiology
Genetics
Molecular Biology
Physiology
Chemical Sciences not elsewhere classified
Immunology
Biological Sciences not elsewhere classified
Marine Biology
Taylor & Francis
2022
2022-01-18
2024-03-21
Journal contribution
523950 Bytes
10.6084/m9.figshare.18586089
10.1080/21655979.2021.2017698
CC BY 4.0