Long noncoding RNA MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability.

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is implicated in liver cell proliferation. However, its role in hepatic steatosis and insulin resistance remain poorly understood. The aim of this study was to investigate the effects of MALAT1 on hepatic lipid accumulation and its potential targets. As expected, MALAT1 expression is increased in hepatocytes exposed to palmitate and livers of ob/ob mice. Knockdown of MALAT1 expression dramatically suppressed palmitate-induced lipid accumulation and the increase of nuclear SREBP-1c protein in HepG2 cells. In addition, RNA immunoprecipitation and RNA pull-down assay confirmed that MALAT1 interacted with SREBP-1c to stabilize nuclear SREBP-1c protein. Finally, injection of si-MALAT1 prevented hepatic lipid accumulation and insulin resistance in ob/ob mice. In conclusion, our observations suggest that MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability.

• Authors: Caifeng Yan, Jinfeng Chen, Nuoqi Chen
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 22640 (Mar 03 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26935028 (Publication Type: Journal Article)

Chemical References

• MALAT1 long non-coding RNA, human
• Malat1 long non-coding RNA, mouse
• RNA, Long Noncoding
• SREBF1 protein, human
• Srebf1 protein, mouse
• Sterol Regulatory Element Binding Protein 1

Topics

• Animals
• Cell Nucleus (genetics, metabolism)
• Fatty Liver (genetics, metabolism, pathology)
• Hep G2 Cells
• Humans
• Lipid Metabolism
• Mice
• Mice, Obese
• Protein Stability
• RNA, Long Noncoding (genetics, metabolism)
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)