Spirulina liquid extract regulates gene expression related to glucose and lipid metabolisms of soleus muscle during exercise training in young male Wistar rats fed a high-fat diet

• Spirulina liquid extract (SLE) has beneficial effects on soleus muscle glucose and lipid metabolism. • SLE reduces glycemia, upregulates Gys1 and downregulates IRS1 expressions. • SLE combined with training increases HDL-chol, reduces non-HDL-chol. • SLE upregulates CPT1A and downregulates Fabp4 gene expressions. Metabolic disorders induced by high-fat diets (HFD) contribute to obesity, diabetes, and cardiovascular diseases. While Spirulina liquid extract (SLE) has shown promise in improving lipid accumulation and insulin resistance, in vivo evidence remains limited, particularly in combination with exercise. Muscle activity is a key regulator of metabolism, but the potential combined effect of SLE and physical training under HFD conditions has not been established. In this study, young male rats were fed a HFD (60 % energy from lipids) and assigned to four groups: HFD with 10% fructose (HF f ), HF f with SLE (HF f SP), HF f with exercise (HF f T), and HF f with both interventions (HF f SPT). Bodyweight (BW), lipid profiles, glycemia regulation, and gene expression in soleus muscle (SOL) of lipid and glucose metabolism were assessed. SLE reduced fasting glycemia compared to the HF f group (1.19-fold) and upregulated Gys1 (1.78-fold) and CPT1A expression (4.13-fold) in SOL. Training improved glucose tolerance, as reflected by reduced AUC (p = 0.01), and upregulated PGC1⍺ and CPT1A expression. The combined intervention (HF f SPT) decreased BW, increased HDL-cholesterol (1.62-fold), reduced the atherogenic index (AIP) (1.39-fold). During training conditions, PGC1⍺ expression was downregulated by SLE (3.03-fold), suggesting a possible interference with exercise-induced muscle adaptation. p38 MAPK, elevated by HFD, was downregulated by SLE, exercise, and their combination (3.20-, 5.14-, and 2.72-fold, respectively). Overall, these findings support the potential of SLE as a complementary strategy to exercise in attenuating HFD-induced metabolic dysfunctions, while also raising concerns about possible interference with training adaptations. Evaluation of Spirulina liquid extract on Wistar rats fed a high-fat diet during 8 weeks of exercise. In skeletal muscle, the extract showed effects similar to exercise on glycogen storage. Combined, it enhanced the gene expression related to fatty acid oxidation and glucose storage. IRS1: Insulin Receptor Substrate 1, GLUT4: Glucose Transporter Type 4, Gys1: Glycogen Synthase 1, CD36: Cluster of Differentiation 36, Fabp4: Fatty Acid Binding Protein 4, CPT1A: Carnitine Palmitoyltransferase 1A.