Tirzepatide administration improves cognitive impairment in HFD mice by regulating the SIRT3-NLRP3 axis.

PURPOSE: High-fat diet (HFD) currently is reported that in connection with cognitive impairment. Tirzepatide is a novel dual receptor agonist for glycemic control. But whether Tirzepatide exerts a protective effect in HFD-related cognitive impairment remains to be explore. METHODS: During the study, the cognitive dysfunction mice model induced by HFD were established. The expressions synapse-associated protein and other target proteins were detected. The oxidative stress parameters, levels of inflammatory cytokine were also detected. RESULTS: Our findings proved that Tirzepatide administration attenuates high fat diet-related cognitive impairment. Tirzepatide administration suppresses microglia activation, alleviates oxidative stress as well as suppressed the expression of NLRP3 in HFD mice by up-regulating SIRT3 expression. In conclusion, Tirzepatide attenuates HFD-induced cognitive impairment through reducing oxidative stress and neuroinflammation via SIRT3-NLRP3 signaling. CONCLUSION: This study suggest that Tirzepatide has neuroprotective effects in HFD-related cognitive dysfunction mice model, which provides a promising treatment of HFD-related cognitive impairment.