Comparison of lncRNA and mRNA expression profile among the livers of C57BL/6J control mice, high fat diet (HFD) mice and metformin treated mice

Nonalcoholic fatty liver disease (NAFLD) is a growing worldwide epidemic and an important risk factor for the development of insulin resistance, type 2 diabetes, nonalcoholic steatohepatitis (NASH), and hepatic cellular carcinoma (HCC). Despite the prevalence of NAFLD, lifestyle interventions involving exercise and weight loss are the only accepted treatments for this disease. Over the past years, metformin has been shown to improve NAFLD in preclinical animal models. However, whether and how the long non-coding RNAs (lncRNAs) were involved in the progression of NAFLD and the mechanism of metformin treatment were not clearly understood. The aim of this study was to identify lncRNAs associated with the regulation of liver lipid metabolism after metformin treatment. We performed computational analysis of the function enrichment of the differentially expressed lncRNAs and mRNAs. Our analysis also suggested significant co-expression between hepatic lncRNAs and their predicted mRNA targets. Our analysis suggests a noticeable role in the etiology and treatment of NAFLD. Three-week-old wild-type C57BL/6J mice were purchased from the Spfanimals Company (Beijing, China). These mice were divided into three groups: the control group (C), the high fat diet group (H) and the metformin treated (M) group. For the normal control (C) group, the mice were maintained with chow diet for 17 weeks. For the high fat diet (H) and metformin treated (M) group, C57BL/6J mice were fed a high fat diet (HFD, D12451, 45% kcal from fat, Research Diet, USA, http://www.researchdiets.com/opensource-diets/stock-diets) for 17 weeks. Starting at the 15 weeks old of age (i.e. after 12 weeks of high fat diet feeding), the high fat diet (H) and metformin treated (M) group were differentially treated: the mice from metformin treated (M) group were intragastrically treated with 3 mg/kg/day metformin for 5 weeks; while those from the high fat diet (H) group were treated with saline vehicle for 5 weeks. Finally, the liver tissue from different groups of mice were collected respectively at the 20 weeks old of age, and the lncRNA and mRNA expression profiles were measured using the CapitalBiotech mouse lncRNA+mRNA v1.0 microarray. Three biological replicates were prepared for each group. It is noteworthy that each biological replicate contains a mixed liver tissue samples collected from four mice of the same group.