Taurine and High-Intensity Interval Training Modulate TXNIP–PI3K/AKT Signaling in Male C57BL/6J Mice with High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease

Introduction: Non-alcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance and chronic low-grade inflammation. Exercise training and taurine supplementation have emerged as promising strategies to improve metabolic function by modulating insulin signaling and inflammatory pathways. This study investigated the effects of taurine supplementation and high-intensity interval training (HIIT), alone and in combination, on insulin signaling and inflammasome-related pathways in a high-fat diet (HFD)-induced mouse model of NAFLD. Methods: Fifty-six male C57BL/6J mice were assigned to either a control diet (CON, n = 8) or an HFD (n = 48). After 12 weeks, HFD-fed mice were randomized into six groups: HFD, HFD+HIIT (HE), HFD+2.5% taurine (HT-2.5), HFD+HIIT+2.5% taurine (HET-2.5), HFD+5% taurine (HT-5), and HFD+HIIT+5% taurine (HET-5) (n = 8/group). Interventions were performed concurrently for 10 weeks. Results: Compared with controls, HFD-fed mice exhibited increased HOMA-IR, impaired PI3K/AKT signaling, elevated PTEN expression, and increased hepatic TXNIP, NLRP3, and caspase-1 levels (all p < 0.05). All intervention groups improved HOMA-IR and reduced PTEN, TXNIP, and caspase-1 expression compared with the HFD group (p < 0.05). PI3K phosphorylation increased only in the HET-2.5 group, whereas AKT phosphorylation increased in the HE, HT-5, and HET-2.5 groups (p < 0.05). Notably, concurrent enhancement of both PI3K and AKT phosphorylation was observed exclusively in the HET-2.5 group. Conclusion: HIIT and taurine supplementation improved metabolic and inflammatory alterations associated with HFD-induced NAFLD. These findings support the potential of combined exercise and nutritional interventions as complementary strategies for mitigating metabolic dysfunction associated with NAFLD and warrant further clinical investigation.