論文 - 詳細
| RRC ID | 59397 |
|---|---|
| 著者 | Perez-Gomez A, Carretero M, Weber N, Peterka V, To A, Titova V, Solis G, Osborn O, Petrascheck M. |
| タイトル | A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia. |
| ジャーナル | Nat Commun |
| Abstract |
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. |
| 巻・号 | 9(1) |
| ページ | 5272 |
| 公開日 | 2018-12-10 |
| DOI | 10.1038/s41467-018-07684-y |
| PII | 10.1038/s41467-018-07684-y |
| PMID | 30532051 |
| PMC | PMC6288085 |
| MeSH | Animals Antipsychotic Agents / toxicity CCAAT-Binding Factor / genetics Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Chemotherapy, Adjuvant DNA-Binding Proteins / genetics Eating / drug effects Eating / genetics* Gene Expression / drug effects Gene Expression Profiling Hyperphagia / chemically induced Hyperphagia / drug therapy Hyperphagia / genetics* Hypothalamus / metabolism Mice Phenotype Transcription Factors / genetics Vemurafenib / pharmacology |
| IF | 11.878 |
| 引用数 | 5 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 21 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1325 tm1062 tm1392 tm4257 tm4760 tm3224 tm1265 tm2908 tm3026 |