A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila.

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. Manipu

SUBMITTER: Beshel J 

PROVIDER: S-EPMC5235317 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature