Difference Analysis of MiRNA Expression Profiles in Aged Female Rat Adipose Tissue Regulated by HIIT and MICT.

Abstract

Aging is frequently associated with dysregulated lipid metabolism, while exercise may improve metabolic health, a process in which microRNAs (miRNAs) play a pivotal regulatory role. However, the specific modulation of miRNA expression profiles by different exercise modalities remains poorly characterized. This study aimed to investigate adipose tissue miRNA profiles in aged rats following high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Eighteen-month-old female rats were divided into three groups (n = 12/group): sedentary (SED), MICT, and HIIT. After 8 weeks of exercise interventions, metabolic outcomes were assessed using Oil Red O staining to quantify intracellular lipid deposition, alongside Western blotting, immunofluorescence, and RT-qPCR to evaluate mRNA and protein expression of adipose tissue markers. Additionally, miRNA sequencing was performed on visceral adipose tissue to identify differentially expressed miRNAs (DEMs), followed by bioinformatic prediction of miRNA-mRNA interactions. Key findings revealed that the HIIT group exhibited more pronounced metabolic benefits compared to MICT, including reduced lipid accumulation (fewer Oil Red O-positive adipocytes) and upregulated expression of lipolytic and autophagy-related proteins (ATGL, HSL, PPAR-γ, ATG3, ATG5, ATG7, ATG12, and ATG16L). miRNA sequencing demonstrated greater divergence in expression profiles between HIIT and SED groups than between MICT and SED groups. KEGG pathway analysis highlighted significant enrichment in the MAPK, PI3K-Akt, and Rap1 signaling pathways. Furthermore, 11 DEMs (e.g., miR-34a, miR-146a) were identified as potential regulators of adipose aging, with hub genes including Shc1, Grb2, Itgb1, Ptpn11, Mapk14, Fyn, Plcg1, Sos1, and Actg1. In conclusion, HIIT significantly ameliorates age-related adipocyte inflammation and metabolic dysfunction. Exercise-induced miRNA reprogramming may alleviate the functional decline of aged adipose tissue, and HIIT-induced miRNA reprogramming is more abundant. The miRNA sequencing data pinpoint critical regulatory genes and pathways, providing novel insights into the molecular mechanisms by which exercise counteracts metabolic abnormalities in aged adipose tissue.