Brain adiponectin signaling controls peripheral insulin response in Drosophila

Nat Commun. 2021 Sep 24;12(1):5633. doi: 10.1038/s41467-021-25940-6.

Abstract

The brain plays a key role in energy homeostasis, detecting nutrients, metabolites and circulating hormones from peripheral organs and integrating this information to control food intake and energy expenditure. Here, we show that a group of neurons in the Drosophila larval brain expresses the adiponectin receptor (AdipoR) and controls systemic growth and metabolism through insulin signaling. We identify glucose-regulated protein 78 (Grp78) as a circulating antagonist of AdipoR function produced by fat cells in response to dietary sugar. We further show that central AdipoR signaling inhibits peripheral Juvenile Hormone (JH) response, promoting insulin signaling. In conclusion, we identify a neuroendocrine axis whereby AdipoR-positive neurons control systemic insulin response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Brain / cytology
  • Brain / metabolism*
  • Cell Line
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Energy Metabolism / genetics
  • Hemolymph / metabolism
  • Homeostasis
  • Insulin / metabolism*
  • Juvenile Hormones / metabolism
  • Larva / genetics
  • Larva / metabolism
  • Neurons / metabolism*
  • Receptors, Adiponectin / genetics
  • Receptors, Adiponectin / metabolism*
  • Signal Transduction / genetics

Substances

  • Drosophila Proteins
  • Insulin
  • Juvenile Hormones
  • Receptors, Adiponectin