| Autor: |
Perez-Gomez, Anabel, Carretero, Maria, Weber, Natalie, Peterka, Veronika, To, Alan, Titova, Viktoriya, Solis, Gregory, Osborn, Olivia, Petrascheck, Michael |
| Zdroj: |
Nature Communications; 12/10/2018, Vol. 9 Issue 1, p1-1, 1p |
| Abstrakt: |
Antipsychotic (AP) drugs are used to treat psychiatric disorders but are associated with significant weight gain and metabolic disease. Increased food intake (hyperphagia) appears to be a driving force by which APs induce weight gain but the mechanisms are poorly understood. Here we report that administration of APs to C. elegans induces hyperphagia by a mechanism that is genetically distinct from basal food intake. We exploit this finding to screen for adjuvant drugs that suppress AP-induced hyperphagia in C. elegans and mice. In mice AP-induced hyperphagia is associated with a unique hypothalamic gene expression signature that is abrogated by adjuvant drug treatment. Genetic analysis of this signature using C. elegans identifies two transcription factors, nhr-25/Nr5a2 and nfyb-1/NFYB to be required for AP-induced hyperphagia. Our study reveals that AP-induced hyperphagia can be selectively suppressed without affecting basal food intake allowing for novel drug discovery strategies to combat AP-induced metabolic side effects. The molecular pathway(s) driving antipsychotics (AP) induced hyperphagia remains unclear. A novel C. elegans system is used here to screen for FDA approved drugs that selectively suppresses this response, unraveling potential molecular mediators influencing AP induced hyperphagia in mouse models. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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