Cholecystokinin-like peptide mediates satiety by inhibiting sugar attraction

PLoS Genet. 2021 Aug 16;17(8):e1009724. doi: 10.1371/journal.pgen.1009724. eCollection 2021 Aug.

Abstract

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Carbohydrate Metabolism / physiology
  • Carbohydrates / physiology
  • Cholecystokinin / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Feeding Behavior / physiology*
  • Feeding Behavior / psychology
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics
  • Hemiptera / genetics
  • Hemiptera / physiology
  • Neurons / metabolism
  • Neuropeptides / metabolism
  • Receptors, Cell Surface / genetics
  • Starvation / metabolism
  • Sugars / metabolism
  • Taste / physiology
  • Taste Perception / genetics*
  • Taste Perception / physiology

Substances

  • Carbohydrates
  • Neuropeptides
  • Receptors, Cell Surface
  • Sugars
  • Cholecystokinin

Grants and funding

This work was supported by the National Natural Science Foundation of China to SFW (No. 32022011 & 31772205) (https://isisn.nsfc.gov.cn/egrantindex/funcindex/prjsearch-list?locale=zh_CN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.