ArticleCell metabolism2017
A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 76 citations in OpenAlex.
- A Tale of Two States: Similarities and Differences in Neuropeptide Signaling in Larval and Adult Drosophila.The Journal of comparative neurology · 2026Review
- Sex-biased expression of enteroendocrine cell-derived hormones contributes to higher fat storage ineLife · 2026Article
- Sex-specific metabolic regulation by the Drosophila RNA-binding protein Nab2.bioRxiv : the preprint server for biology · 2026Article
- Cellular source and circuit context organize functional specificity in thebioRxiv : the preprint server for biology · 2026Article
- Cell-type-resolved RNA-seq reveals molecular signatures of sexual experience inNAR genomics and bioinformatics · 2026Article
- Tumor-induced orexigenic imbalance lowers protein appetite and drives early organ wasting symptoms.Nature communications · 2026Article
- The RASA2/RASA3 ortholog RasGAP1 modulates obesity-linked phenotypes and is associated with leptin-analog signaling inFrontiers in endocrinology · 2026Article
- Gut-brain communication in Drosophila melanogaster.Current opinion in neurobiology · 2025Review
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- Insulin/insulin-like growth factor signaling pathway promotes higher fat storage inbioRxiv : the preprint server for biology · 2025Article
- Glycolytic disruption restricts Drosophila melanogaster larval growth via the cytokine Upd3.PLoS genetics · 2025Article
- Review
- Review
- Reciprocal interactions between neuropeptide F and RYamide regulate host attraction in the mosquitoProceedings of the National Academy of Sciences of the United States of America · 2024Article
- The sex of organ geometry.Nature · 2024Article
- A Skeletal Muscle-Centric View on Time-Restricted Feeding and Obesity under Various Metabolic Challenges in Humans and Animals.International journal of molecular sciences · 2022Review
- Neural Control of Action Selection Among Innate Behaviors.Neuroscience bulletin · 2022Review
- Of flies, mice and neural control of food intake: lessons to learn from both models.Current opinion in neurobiology · 2022Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Leptin, a typically adipose-derived "satiety hormone," has a well-established role in weight regulation. Here we describe a functionally conserved model of genetically induced obesity in Drosophila by manipulating the fly leptin analog unpaired 1 (upd1). Unexpectedly, cell-type-specific knockdown reveals upd1 in the brain, not the adipose tissue, mediates obesity-related traits. Disrupting brain-derived upd1 in flies leads to all the hallmarks of mammalian obesity: increased attraction to food cues, increased food intake, and increased weight. These effects are mediated by domeless receptors on neurons expressing Drosophila neuropeptide F, the orexigenic mammalian neuropeptide Y homolog. In vivo two-photon imaging reveals upd1 and domeless inhibit this hedonic signal in fed animals. Manipulations along this central circuit also create hypersensitivity to obesogenic conditions, emphasizing the critical interplay between biological predisposition and environment in overweight and obesity prevalence. We propose adipose- and brain-derived upd/leptin may control differing features of weight regulation through distinct neural circuits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.