Abstract

Hyperlipidemia is a risk factor for cardiovascular disease, and miR-21a-5p plays an important role in the occurrence and progression of hyperlipidemia. Here, we aimed to investigate the mechanism of aerobic exercise improved hyperlipidemia through enhancing miR-21a-5p expression. In this study, high-fat/high-cholesterol diet mice received 8 weeks of aerobic exercise intervention, then we collected plasma and liver samples, we found that there had a notable improvement in weight gain, blood lipid level, and liver steatosis in hyperlipidemia mice after 8 weeks of aerobic exercise intervention. Besides, aerobic exercise significantly up-regulated the expression of miR-21a-5p and provoked favorable changes in the expression of target genes. Knockdown of miR-21a-5p resulted in dysregulation of lipid metabolism and increased expression of FABP7, HMGCR, ACAT1, and OLR1. While aerobic exercise could alleviate miR-21a-5p knock-down induced lipid metabolism disorder. Taken together, these results demonstrated that aerobic exercise improved hyperlipidemia through miR-21a-5p-induced inhibition of target genes FABP7, HMGCR, ACAT1, and OLR1.

Highlights

  • Hyperlipidemia is a risk factor for cardiovascular disease, and miR-21a-5p plays an important role in the occurrence and progression of hyperlipidemia

  • We have found that the target genes of miR-21a-5p involved in lipid metabolism, including fatty acid-binding protein 7 (FABP7)7, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)[5], peroxisome proliferator-activated receptor α (PPARα)[8] and phosphatase and tensin homolog deleted on chromosome 10 (PTEN)[9]

  • We think one of the mechanisms by which aerobic exercise improved hyperlipidemia was to up-regulate the expression of miR-21a-5p, inhibited the expression of target genes FABP7, HMGCR, acetyl-CoA acetyltransferase 1 (ACAT1), and oxidized low-density lipoprotein receptor 1 (OLR1), which were closely related to lipid metabolism

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Summary

Introduction

Hyperlipidemia is a risk factor for cardiovascular disease, and miR-21a-5p plays an important role in the occurrence and progression of hyperlipidemia. While aerobic exercise could alleviate miR-21a-5p knock-down induced lipid metabolism disorder. Taken together, these results demonstrated that aerobic exercise improved hyperlipidemia through miR-21a-5p-induced inhibition of target genes FABP7, HMGCR, ACAT1, and OLR1. MiR-21a is one of the first mammalian microRNAs identified, which involves many physiological processes and relates to a variety of diseases, one of its most representative roles is to regulate lipid m­ etabolism[4]. We have found that the target genes of miR-21a-5p involved in lipid metabolism, including fatty acid-binding protein 7 (FABP7)7, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)[5], peroxisome proliferator-activated receptor α (PPARα)[8] and phosphatase and tensin homolog deleted on chromosome 10 (PTEN)[9].

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