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Multi-tissue transcriptomic landscape reveals synergistic mechanisms of exercise and GLP-1 agonist in ameliorating diabetic phenotypes in db/db mice

GSE341948 Mus musculus Expression profiling by high throughput sequencing 12 samples Submitted 2026/08/08 Platform GPL24247

Summary

Type 2 diabetes mellitus (T2DM) involves coordinated multi-organ metabolic dysfunction, yet the systems-level effects of combined pharmacological and exercise interventions remain unclear. Male db/db mice received semaglutide, high-intensity interval training (HIIT), or both for eight weeks. Multi-organ bulk RNA-seq with qPCR validation and CellChat analysis was performed in heart, kidney, liver, hippocampus, and skeletal muscle. Combined treatment produced the greatest reductions in food intake, body weight, and fasting glucose. Transcriptomic responses were organ-dependent, most pronounced in skeletal muscle and liver. Under combination therapy, DEGs in hippocampus and liver no longer reached thresholds relative to single interventions, consistent with unchanged hippocampal Glp1r and hepatic Plpp7 by qPCR, whereas heart, kidney, and skeletal muscle retained concordant regulation with further reductions in cardiac Cyp2ab1 and renal/muscle Apoa1. Cross-organ analysis identified coordinated modulation of the PPARα–Plin4 axis and suppression of lipid metabolic pathways, confirmed by qPCR. Inter-organ network analysis revealed increased communication numbers but reduced interaction strength under combination therapy. These findings demonstrate organ-specific transcriptional adaptation to combined HIIT and semaglutide.

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Direct links to NCBI, no account and no request form: the whole study as GSE341948_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1504874 and SRA study SRP722761. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × liver, db/db control group, vs 3 × liver, exercised,60min, vs 3 × liver, semaglutide,0.05 mg/kg, vs 3 × liver, semaglutide + HIIT, 0.05 mg/kg injection + 60 min exercise,

Supports a between-group comparison across 12 samples.

4 replicated groups read from 12 sample titles; they account for 12 of them. Check it against the sample list below before relying on it.

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