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Tirzepatide administration improves cognitive impairment in HFD mice by regulating the SIRT3-NLRP3 axis
Jingjing Ma1,2, Yuanyuan Liu2, Junya Hu3
1Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, 21006, China.
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.
