Work

Epigenetic Modifications in Alternative Splicing of LDLR pre-mRNA on Hypercholesterolemia Following Aerobic Exercise Training

Year: 2025

Type: article

Abstract: This study investigated whether exercise training improved cholesterol metabolism through modifying alternative splicing of the low-density lipoprotein receptor (LDLR). Blood lipids and expressions of LDLR splice variants were compared between exercise-trained and non-trained young adults with normal and high cholesterol. The expression of LDLR splice isoforms were examined using RT-PCR and the histone H3K36me3 by CHIP-assay in mouse liver following a 13-week normal or high-cholesterol-diet combined with or without 8 weeks of aerobic exercise-training. The influence of histone modifications on LDLR alternative splicing was examined in HepG2 cells (human liver cell-line). Expression levels of LDLR deletions in exons 4 and 12 (LDLR-∆Exon4 and LDLR-∆Exon12) were significantly higher in the obese adults with high-cholesterol. These LDLR splice variants were significantly lower in the exercise-trained than non-trained group with normal cholesterol. Thirteen weeks of high-cholesterol feeding increased LDLR-∆Exon14 expression in mice, which was diminished after 8 weeks of exercise training. When H3-K36me3 or the MORF-related gene on chromosomes 15 were overexpressed and interfered, the levels of LDLR-∆Exon4 and LDLR-∆Exon12 expression in HepG2 cells were significantly augmented and inhibited, respectively. Hypercholesterolemia was associated with augmented expressions of LDLR splice variants in obese adults and following high-cholesterol diet in mice. Aerobic exercise training prevented and reversed the dyslipidemia-related alternative splicing of LDLR pre-mRNA. The histone modifications contributed to the alternative splicing.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26094262

Authors: Jinfeng Zhao, Peirun Yan, Yana Pang, Yuankun Dong, Xiangrong Shi

Institutions: University of North Texas, University of North Texas Health Science Center, Shanxi University, Shanxi Medical University

Language: English

Topic: Cholesterol and Lipid Metabolism

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499