ABSTRACT
Purpose@#This research was designed to investigate how miR-542-5p regulates the progression of hyperglycemia and hyperlipoidemia. @*Materials and Methods@#An in vivo model with diabetic db/db mice and an in vitro model with forskolin/dexamethasone (FSK/DEX)-induced primary hepatocytes and HepG2 cells were employed in the study. Bioinformatics analysis was conducted to identify the expression of candidate miRNAs in the liver tissues of diabetic and control mice. H&E staining revealed liver morphology in diabetic and control mice. Pyruvate tolerance tests, insulin tolerance tests, and intraperitoneal glucose tolerance test were utilized to assess insulin resistance. ELISA was conducted to evaluate blood glucose and insulin levels. Red oil O staining showed lipid deposition in liver tissues. Luciferase reporter assay was used to depict binding between miR-542-5p and forkhead box O1 (FOXO1). @*Results@#MiR-542-5p expression was under-expressed in the livers of db/db mice. Further in vitro experiments revealed that FSK/DEX, which mimics the effects of glucagon and glucocorticoids, induced cellular glucose production in HepG2 cells and in primaryhepatocytes cells. Notably, these changes were reversed by miR-542-5p. We found that transcription factor FOXO1 is a target of miR-542-5p. Further in vivo study indicated that miR-542-5p overexpression decreases FOXO1 expression, thereby reversing increases in blood glucose, blood lipids, and glucose-related enzymes in diabetic db/db mice. In contrast, anti-miR-542-5p exerted an adverse influence on blood glucose and blood lipid metabolism, and its stimulatory effects were significantly inhibited by sh-FOXO1 in normal control mice. @*Conclusion@#Collectively, our results indicated that miR-542-5p inhibits hyperglycemia and hyperlipoidemia by targeting FOXO1.
ABSTRACT
Ionomics is a new multidisciplinary scientific field for investigating the composition and distribution of all chemical elements in specific biological systems as well as their variations under different physiological and pathological conditions. It combines both high-throughput techniques for element profile measurement and bioinformatic methods, which provides new ideas for obtaining a systems-level understanding of biological utilization and functions of these elements. More and more results of researches suggest that ionomics has important theoretical and practical values in etiological study, early diagnosis and screening, and therapeutic strategy selection for complex diseases. In this review, we focus on current advances in the ionomic studies of several complex diseases, which may help further understand the effect and important properties of individual elements, as well as their dynamic ionomic networks in the occurrence and development of diseases.