# Transcriptomic Analysis of High-Intensity Interval Training in High-Fat-Diet-Induced Spontaneous Hypertensive Rats’ Brains

**Authors:** Arslan Sadiq, Iqbal Ali Shah, Bor-Tsang Wu, Yi-Yuan Lin, Yi-An Su, Ai-Lun Yang, Shin-Da Lee

PMC · DOI: 10.3390/ijms27010304 · International Journal of Molecular Sciences · 2025-12-27

## TL;DR

This study shows that high-intensity interval training in hypertensive rats reduces brain cell death and improves memory and circadian rhythms.

## Contribution

The study reveals novel transcriptomic effects of HIIT on apoptosis, autophagy, and brain function in hypertensive rats.

## Key findings

- HIIT modulates 1223 genes in hypertensive rats' brains, with 51 showing strong significance.
- Key genes linked to apoptosis and autophagy are altered, including seven downregulated and one upregulated.
- HIIT improves circadian rhythm, long-term memory processes, and hypoxia response in hypertensive brains.

## Abstract

Hypertension contributes to brain dysfunction through apoptosis, oxidative stress, reduced neuronal connectivity, and neurotransmitter imbalance. Exercise training is a non-pharmacological strategy known to modulate these molecular alterations. This study investigated the effects of high-intensity interval training (HIIT) on transcriptomic changes in the cerebral cortex of spontaneously hypertensive rats (SHR) fed a high-fat diet (HFD). Rats were assigned to either a HIIT intervention group (HIIT-HFD-SHR) or a sedentary control group (HFD-SHR). Cortical RNA was extracted, sequenced using the Illumina NovaSeq 6000 platform, and analyzed with DESeq2. Functional enrichment was conducted using Metascape. RNA-seq identified 1223 differentially expressed genes (DEGs) (adjusted p < 0.05), with 51 remaining significant under stringent criteria (adjusted p < 0.001, |log2FC| > 0.5). Among these, eight key genes were closely associated with the regulation of apoptosis and autophagy, including seven downregulated (Egr1, Atf3, Tgm2, Lgals1, Nr4a1, Plekhf1, Nupr1) and one upregulated (Trim39). This transcriptomic analysis following HIIT also modulated circadian rhythm, long-term memory processes, and hypoxia response in the hypertensive brain. These findings indicate that HIIT decreases apoptosis and autophagy and improves circadian rhythm, long-term memory, and hypoxia in hypertensive rats’ brains.

## Linked entities

- **Genes:** EGR1 (early growth response 1) [NCBI Gene 1958], ATF3 (activating transcription factor 3) [NCBI Gene 467], TGM2 (transglutaminase 2) [NCBI Gene 7052], LGALS1 (galectin 1) [NCBI Gene 3956], NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164], PLEKHF1 (pleckstrin homology and FYVE domain containing 1) [NCBI Gene 79156], NUPR1 (nuclear protein 1, transcriptional regulator) [NCBI Gene 26471], TRIM39 (tripartite motif containing 39) [NCBI Gene 56658]

## Full-text entities

- **Genes:** Tgm2 (transglutaminase 2) [NCBI Gene 56083] {aka TGII, TgaseII, tTG}, Trim39 (tripartite motif-containing 39) [NCBI Gene 309591] {aka Rnf23}, Egr1 (early growth response 1) [NCBI Gene 24330] {aka Krox-24, NGFI-A, Ngf1, Ngfi, zif-268}, Lgals1 (galectin 1) [NCBI Gene 56646], Nr4a1 (nuclear receptor subfamily 4, group A, member 1) [NCBI Gene 79240] {aka HMR, Ngfi-b, Nur77}, Plekhf1 (pleckstrin homology and FYVE domain containing 1) [NCBI Gene 308543], Atf3 (activating transcription factor 3) [NCBI Gene 25389] {aka LRF-1, LRFI}, Nupr1 (nuclear protein 1, transcriptional regulator) [NCBI Gene 100912108] {aka Nupr1l1, p8}
- **Diseases:** brain dysfunction (MESH:D001927), hypoxia (MESH:D000860), Hypertension (MESH:D006973)
- **Chemicals:** Fat (MESH:D005223)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12785774/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12785774/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12785774/full.md

---
Source: https://tomesphere.com/paper/PMC12785774