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For example, in Glp1r Nes–/– mice, semaglutide loses its acute antiinflammatory effects against LPS-induced inflammation, yet tirzepatide still effectively prevents TNF-α induction, suggesting that tirzepatide does not rely exclusively on neuronal GLP-1R to exert this effect (22)
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Some studies have demonstrated the ability of gut-derived GLP-1 to cross through the blood-brain barrier and thoroughly perfuse the brain parenchyma, but whether its effects are similar to that of PPG-derived GLP-1 remains to be established [50, 53]
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