Circulating miR-27a-3p as a candidate for a biomarker of whole grain diets for lipid metabolism

Abstract

As a worldwide epidemic, overweight and obesity have long been an issue of great interest in a wide range of health areas, and the whole grain diet has been proven to be an effective and healthy manner to prevent them. Recent developments in the field of microRNAs (miRNAs) have led to a renewed interest in lipid metabolism, however, whether a whole grain diet regulates lipid metabolism through miRNAs is still unknown. Hence, our current study was carried out to explore the changes of miRNAs in mice with the treatment of whole grain diets (the brown rice group, BR and whole wheat group, WW) and to screen out miRNAs that can serve as a biomarker to evaluate and regulate lipid metabolism. After whole grain diet treatment for 8 weeks, the lipids both in serum and liver were reduced, as well as the body weight. Moreover, there were 136 miRNAs with significant differences among our three dietary patterns (the CS diet, BR diet and WW diet) analyzed by serum miRNAs sequencing, and only 16 miRNAs showed simultaneous differences in the BR or WW groups compared to the CS group, showing a consistent trend of change. The serum miRNA sequencing and qRT-PCR analysis revealed that miR-27a-3p was decreased in serum and WAT, while it was elevated both in the liver and ileum. We propose that circulating miR-27a-3p could be a novel candidate for a biomarker of whole grain diets for lipid metabolism through the assessment of the KEGG pathway, GO enrichment and the conservative analysis of miRNAs. The potential mechanisms of action could be through binding the 3′UTR of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and fatty acid synthase (FASN), which were key enzymes for lipid synthesis, achieving regulation of lipid metabolism. A luciferase assay was also performed to verify the above mechanism, which shows that miR-27a-3p mimics transfection, repressing the luciferase activity of the two reporters carrying miR-27a-3p regulatory elements found in the 3′-UTR of HMGCR and FASN, respectively. Our study has provided new molecular mechanisms of whole grain diets for lipid metabolism, as well as a new therapeutic target for the treatment of obesity.