HOTAIR participates in hepatic insulin resistance via regulating SIRT1.

Abstract

The aim of this study was to investigate the effect of long non-coding RNA (lncRNA) HOTAIR on hepatic insulin resistance and to explore the possible underlying mechanism. Liver tissues of type 2 diabetes mellitus (T2D) patients, healthy controls, C57BL/6J mice fed with a high-fat diet and db/db mice were harvested. Meanwhile, the expressions of HOTAIR and SIRT1 were detected. Subsequently, We HepG2 cells were treated with tumor necrosis factor α (TNF-α), and the insulin resistance model was constructed in vitro. The mRNA expression levels of HOTAIR and SIRT1 in the insulin resistance model were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Insulin sensitivity in HepG2 cells transfected with lentivirus was evaluated by relative commercial kits. In addition, protein expression levels of key factors in the AKT/GSK pathway were detected by Western blot. HOTAIR was significantly upregulated in T2D patients, C57BL/6J mice fed with a high-fat diet and db/db mice. However, SIRT1 expression presented an opposite changing trend. Moreover, upregulated HOTAIR remarkably promoted hepatic insulin resistance via the AKT/GSK pathway, which could be reversed by SIRT1 overexpression. Upregulated HOTAIR promotes hepatic insulin resistance by inhibiting SIRT1 expression and AKT/GSK pathway.