Exosomal MicroRNA Expression Profiling Analysis of the Effects of Lycium Barbarum Polysaccharide on Gestational Diabetes Mellitus Mice

Abstract

OBJECTIVE: Gestational diabetes mellitus (GDM) is a pathological condition, affecting an increasing number of pregnant women worldwide. Safe and effective treatment for GDM is very important for the public health. In this study, we utilized a high-fat diet-induced GDM model to evaluate the effects of LBP on GDM and examined the changes of exosomal microRNA expression profiling to decipher the potential underlying mechanism of LBP. METHODS: Female C57BL/6J mice were fed a control diet, HFD, or 150 mg/kg LBP-supplemented HFD for 6 weeks before conception and throughout gestation. Oral glucose tolerance test and plasma lipid levels were determined, and liver histopathology was assessed. Sequencing was used to define the microRNA expression profiling of plasma exosomes in the three groups of mice, and protein expression levels of the candidate target genes were analyzed. RESULTS: LBP significantly relieved glucose intolerance, abnormal plasma lipid levels, and pathomorphological changes of liver histopathology in HFD-induced GDM mice. Moreover, we found that this effect of LBP was mediated by downregulation of the increase of 6 miRNAs (miR-93-3p, miR-188-5p, miR-466k, miR-1188-5p, miR-7001-3p, and miR-7115-5p) and reversing the increase of the protein expression of CPT1A, which is the target gene of miR-188-5p. CONCLUSIONS: Our findings provide novel insights into the biological activities of LBP in the treatment of GDM.