Reference - Detail
| RRC ID | 59397 |
|---|---|
| Author | Perez-Gomez A, Carretero M, Weber N, Peterka V, To A, Titova V, Solis G, Osborn O, Petrascheck M. |
| Title | A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia. |
| Journal | 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. |
| Volume | 9(1) |
| Pages | 5272 |
| Published | 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 |
| Times Cited | 5 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 21 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1325 tm1062 tm1392 tm4257 tm4760 tm3224 tm1265 tm2908 tm3026 |