Ni Pinshi, Su Yingmin, Wang Zhuangzhi, Cui Jianmei, Lu Peng, Li Fanghui
School of Sport Sciences, Nanjing Normal University, Nanjing, China.
Institute of Physical Education, North University of China, Taiyuan, China.
Cell Biochem Biophys. 2025 Apr 18. doi: 10.1007/s12013-025-01757-8.
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.
衰老常与脂质代谢失调相关，而运动可改善代谢健康，在此过程中微小RNA（miRNA）发挥着关键的调节作用。然而，不同运动方式对miRNA表达谱的具体调节作用仍不清楚。本研究旨在调查高强度间歇训练（HIIT）和中等强度持续训练（MICT）后老年大鼠脂肪组织中的miRNA谱。将18月龄雌性大鼠分为三组（每组n = 12）：久坐不动组（SED）、MICT组和HIIT组。经过8周的运动干预后，使用油红O染色评估代谢结果以量化细胞内脂质沉积，同时采用蛋白质免疫印迹法、免疫荧光法和逆转录定量聚合酶链反应（RT-qPCR）来评估脂肪组织标志物的mRNA和蛋白质表达。此外，对内脏脂肪组织进行miRNA测序以鉴定差异表达的miRNA（DEM），随后对miRNA-mRNA相互作用进行生物信息学预测。主要研究结果显示，与MICT组相比，HIIT组表现出更显著的代谢益处，包括脂质积累减少（油红O阳性脂肪细胞减少）以及脂解和自噬相关蛋白（ATGL、HSL、PPAR-γ、ATG3、ATG5、ATG7、ATG12和ATG16L）的表达上调。miRNA测序表明，HIIT组与SED组之间的表达谱差异大于MICT组与SED组之间的差异。京都基因与基因组百科全书（KEGG）通路分析突出了丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）和Rap1信号通路的显著富集。此外，鉴定出11种DEM（如miR-34a、miR-146a）为脂肪衰老的潜在调节因子，其中关键基因包括Shc1、Grb2、Itgb1、Ptpn11、Mapk14、Fyn、Plcg1、Sos1和Actg1。总之，HIIT可显著改善与年龄相关的脂肪细胞炎症和代谢功能障碍。运动诱导的miRNA重编程可能减轻老年脂肪组织的功能衰退，且HIIT诱导的miRNA重编程更为丰富。miRNA测序数据确定了关键调控基因和通路，为运动对抗老年脂肪组织代谢异常的分子机制提供了新见解。
