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
|
リソース情報 |
線虫 |
tm1325
tm1062
tm1392
tm4257
tm4760
tm3224
tm1265
tm2908
tm3026 |