GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330511/primaryOK200TranscriptomicsCaenorhabditis elegansExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330511GEOGSEfalseUncoupling hyperphagia and fat storage by modulation of different serotonergic receptorsPsychotropic drugs such as antipsychotics improve symptoms of psychiatric disorders. However, they are associated with severe metabolic side effects that remodel energy balance, resulting in weight gain and a persistent increase in food intake (hyperphagia). Here, we compare how antipsychotics and exogenous serotonin induce hyperphagia by remodeling energy balance in the nematode C. elegans. We find that the ability of serotonin and antipsychotics to remodel energy balance strictly depends on the serotonergic receptors SER-7 and SER-5, respectively. While both molecules induce hyperphagia, serotonin does so by increasing energy expenditure and reducing fat stores. In contrast, antipsychotics induce hyperphagia and increase fat storage, suggesting that antipsychotic treatment impairs fat storage mediated inhibition of feeding. The modulation of serotonergic signaling by SER-7 and SER-5 enables the manipulation of fat stores independently of feeding, even in hyperphagic animals. Thus, our results uncouple hyperphagia from fat storage and show that continued hyperphagia can be associated with fat gain or fat loss, dependent on the mechanism by which it is induced2026/05/11GSE330511GSM9727920GSM9727922GSM9727911GSM9727910GSM9727921GSM9727913GSM9727902GSM9727923GSM9727912GSM9727904GSM9727915GSM9727914GSM9727903GSM9727917GSM9727906GSM9727916GSM9727905GSM9727919GSM9727908GSM9727907GSM9727918GSM972790918245330511Caenorhabditis elegans