Why does route of administration fundamentally alter olanzapine's metabolic effects from harmful to protective?

neuropsychopharmacology open
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Description

Oral olanzapine causes weight gain and steatosis while i.p. administration prevents these effects and increases energy expenditure. The mechanistic basis for this route-dependent metabolic switch contradicts assumptions about drug effects being dose-dependent rather than delivery-route dependent.

Gap type: contradiction Source paper: Hypothalamic JNK1-hepatic fatty acid synthase axis mediates a metabolic rewiring that prevents hepatic steatosis in male mice treated with olanzapine via intraperitoneal: Additional effects of PTP1B inhibition. (None, None, PMID:37230004)

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