Beshel, J., Dubnau, J., Zhong, Y. (January 2017) A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila. Cell Metab, 25 (1). pp. 208-217. ISSN 1932-7420 (Electronic)1550-4131 (Linking)
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | conserved circuits food intake obesity weight regulation |
| Subjects: | organism description > animal > insect > Drosophila organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits diseases & disorders > nutritional and metabolic diseases > obesity |
| CSHL Authors: | |
| Communities: | CSHL labs > Dubnau lab CSHL labs > Zhong lab |
| Depositing User: | Matt Covey |
| Date: | 10 January 2017 |
| Date Deposited: | 17 Jan 2017 21:16 |
| Last Modified: | 06 Jul 2021 18:41 |
| PMCID: | PMC5235317 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/34030 |
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