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

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 an HFD (60% energy from lipids) and assigned to four groups: HFD with 10% fructose (HF_f), HF_f with SLE (HF_fSP), HF_f with exercise (HF_fT), and HF_f with both interventions (HF_fSPT). Bodyweight, 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 area under the curve (P = .01), and upregulated PGC1⍺ and CPT1A expression. The combined intervention (HF_fSPT) decreased bodyweight, increased high-density lipoprotein-cholesterol (1.62-fold), reduced the atherogenic index of plasma (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.