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Appetite regulating genes in zebrafish gut; a gene expression study.

Ehsan Pashay Ahi1,2, Mathilde Brunel3, Emmanouil Tsakoumis1,4

  • 1Department of Organismal Biology, Comparative Physiology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.

Plos One
|July 19, 2022
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Summary

Leptin signaling influences appetite-regulating genes in the zebrafish gut. Impaired leptin receptors alter the expression of anorexigenic genes, suggesting a role for the gut in feeding regulation.

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Area of Science:

  • Neuroscience
  • Genetics
  • Physiology

Background:

  • The molecular mechanisms of feeding disorders, especially in peripheral organs, are not well understood.
  • While brain-based appetite regulation is known, the gastrointestinal tract's role in feeding control and brain connection is increasingly recognized.
  • Leptin signaling, crucial for body weight and metabolism, acts via its receptor (lepr) in both the brain and gut, but its interaction with other appetite genes in the gut is unclear.

Purpose of the Study:

  • To investigate the gut expression patterns of appetite-regulating genes in zebrafish with impaired leptin receptor function.
  • To explore how different feeding conditions (normal, fasting, refeeding) affect gene expression in the gut.
  • To elucidate the regulatory connections between leptin signaling and anorexigenic genes in the gastrointestinal tract.

Main Methods:

  • Utilized a zebrafish mutant model with a non-functional leptin receptor (lepr).
  • Analyzed the expression of appetite-regulating genes in the zebrafish gut under normal feeding, fasting, and refeeding conditions.
  • Compared gene expression profiles between wild-type and lepr mutant zebrafish.

Main Results:

  • Most appetite-regulating genes are expressed in the zebrafish gut.
  • Orexigenic gene expression showed minimal changes, except for hcrt.
  • Differential expression of 8 anorexigenic genes in wild-types and 4 in lepr mutants was observed following feeding condition changes.
  • Significant differences in anorexigenic gene expression were found between wild-type and lepr mutant zebrafish.
  • Impaired leptin signaling affected regulatory connections among anorexigenic genes in the gut.

Conclusions:

  • Leptin signaling plays a role in regulating feeding behavior through modulation of anorexigenic gene expression in the zebrafish gastrointestinal tract.
  • The gut's role in appetite regulation is further supported by the observed transcriptional changes.
  • Leptin receptor function is critical for the coordinated expression of appetite-related genes in the gut.