Discovery of a gut molecule that flips the feeding-mating switch

On Valentine’s Day, couples around the world will enjoy romantic dinners to celebrate love and relationships. The association between nutrition and mating is not unique to humans, but is reflected in all species of the animal kingdom. However, direct physiological links linking food consumption and reproductive behaviors have not been suspected until recently.

Scientists at the University of California, San Diego who study fruit flies report that a molecule released from the gut after a meal shifts their attention from feeding to mating. Publication on February 9 in the journal Nature, the researchers found that protein-rich foods trigger the release of diuretic hormone 31, or “Dh31,” a signaling molecule that was found to be released from the fly’s gastrointestinal tract. Their identification of Dh31, a neuropeptide believed to be a type of chemical messenger, opens the door to the largely unexplored area of ​​gut-brain communication beyond eating behavior.

Male fruit flies quickly switch from feeding to courtship after consuming protein-rich foods. The amino acids trigger the release of the neuropeptide Dh31 from the gut, which in turn activates Dh31R-expressing neurons in the brain to terminate feeding and initiate courtship through two parallel circuits.

“We found the transition from feeding to mating and were very surprised that a single molecule would have such a profound influence on behavioral decisions,” said Jing Wang, professor of neurobiology in the UC San Diego Division of Biological Sciences and lead author of the study. “Our study provides a mechanistic explanation for how the neuropeptide Dh31 acts on the brain to alter motivation for two evolutionarily critical behaviors.”

In investigating the question of how animals switch from a feeding-focused behavior to a mating mindset, the UC San Diego researchers and their colleagues at UC Santa Cruz used several methods. to arrive at their discovery of the Dh31 molecule, including genetics, three-photon microscopy and fluorescence. imagery.

To confirm their finding, the researchers performed genetic experiments in which Dh31 was knocked out of fruit flies. In these cases, the flies continued to feed and delayed their mating behavior. In other experiments, they activated Dh31 and found that flies quickly turned around to court. Instead of the brain, an area expected for release of the molecule, they found that Dh31 came from the fly’s gut.

“These results indicate that Dh31 is a signaling molecule that reorders the priority of these two opposing behaviors: feeding rather than courtship in the absence of Dh31 and courtship rather than foraging when Dh31 is released from intestine,” Wang said.

The researchers further described parallels with Dh31’s function as a signaling molecule. Orexin, a neuropeptide molecule, has been shown to play a similar role in mammals in the transition from wakefulness to sleep, including rapid eye movement (REM) sleep and non-REM sleep.

These explorations provide insight into decision-making processes as animals shift from behavior that promotes survival, such as foraging, to a different fundamental behavior such as courtship. Wang said their findings only scratched the surface of understanding how gut hormones work beyond diet. Future work will investigate the role of microbiomes in gut-brain communication.

“This work embodies a multidisciplinary approach to understanding behavioral hierarchy at multiple levels, from molecules to neurons and circuit function,” Wang said. “This line of work provides us with an empirical paradigm to study the hierarchical organization of different needs-based behaviors, a framework established by Abraham Maslow 80 years ago to explain the orderly transition of human behaviors.”

The scientists who contributed to the study are: Hui-Hao Lin, Meihua Christina Kuang, Imran Hossain, Yinan Xuan, Laura Beebe (graduate student), Andrew Shepherd, Marco Rolandi and Jing Wang.

Confocal imaging used in the study was supported by the National Institute of Neurological Disorders and Stroke (P30 NS047101; UC San Diego Neuroscience Microscopy Imaging Core). Funding to support the research was provided by the National Science Foundation (1429810) and the National Institutes of Health (R01DK127516, R01DK092640, R01DC009597, and K99DC016338).

With contributions from Susy Kim


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