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microRNA‐141 is associated with hepatic steatosis by downregulating the sirtuin1/AMP‐activated protein kinase pathway in hepatocytes
Author(s) -
Yousefi Zeynab,
Nourbakhsh Mitra,
Abdolvahabi Zohreh,
Ghorbanhosseini SeyedehSara,
Hesari Zahra,
Yarahmadi Sahar,
EzzatiMobasser Samira,
Seiri Parvane,
Borji Mohammad,
Meshkani Reza,
Malek Mojtaba
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29002
Subject(s) - ampk , steatosis , protein kinase a , phosphorylation , hepatocyte , amp activated protein kinase , transfection , fatty liver , hepatic stellate cell , microbiology and biotechnology , luciferase , chemistry , biology , medicine , endocrinology , biochemistry , in vitro , gene , disease
Sirtuin1 (SIRT1) is a crucial regulator of metabolism and it is implicated in the metabolic pathophysiology of several disorders inclusive of Type 2 diabetes and fatty liver disease (NAFLD). The aim of this study was to investigate the role of miR‐141 in hepatic steatosis via regulation of SIRT1/AMP‐activated protein kinase (AMPK) pathway in hepatocytes. Liver hepatocellular cells (HepG2) were treated with high concentration of glucose to be subsequently used for the assessment of miR‐141 and SIRT1 levels in a model of hepatic steatosis. On the other hand, cells were transfected with miR‐141 to investigate its effect on hepatocyte steatosis and viability as well as SIRT1 expression and activity along with AMPK phosphorylation. Targeting of SIRT1 by miR‐141 was evaluated by bioinformatics tools and confirmed by luciferase reporter assay. Following the intracellular accumulation of lipids in HepG2 cells, the level of miR‐141 was increased while SIRT1 mRNA and protein levels, as well as AMPK phosphorylation, was decreased. Transfection with miR‐141 mimic significantly downregulated SIRT1 expression and activity while miR‐141 inhibitor had the opposite effects. Additionally, modulation of miR‐141 levels significantly influenced AMPK phosphorylation status. The results of luciferase reporter assay verified SIRT1 to be directly targeted by miR‐141. miR‐141 could effectively suppress SIRT1 and lead to decreased AMPK phosphorylation in HepG2 cells. Thus, miR‐141/SIRT1/AMPK signaling pathway may be considered a potential target for the therapeutic management of NAFLD.