Feeding behavior is a complex process that is regulated by a variety of factors, including hormones, neurotransmitters, and environmental cues. Recent research has identified two key players in the regulation of feeding behavior: Prolactin-releasing hormone (PRLH) and the caudal nucleus of the solitary tract (cNTS). PRLH neurons are located in the cNTS and are involved in the regulation of both short-term and long-term feeding behavior. In the short term, PRLH neurons respond to the taste and smell of food, as well as to the presence of food in the mouth. This activation leads to the release of prolactin, which in turn stimulates the release of other hormones that promote feeding.
Knight and colleagues have uncovered a pivotal role played by neural circuits in the caudal brainstem, particularly cNTS, in the termination of meals and the regulation of satiety. PRLH neurons were found to exhibit dynamic responses to both oral and visceral stimuli, governing feeding bursts. In contrast, GCG neurons responded to gut feedback, inducing longer-lasting satiety. This study sheds light on the brainstem’s sequential appetite regulation and underscores the importance of further exploration in awake animals.
In a groundbreaking overnight-fasted mouse study, researchers observed rapid activation of PRLH neurons within seconds during self-paced oral consumption of nutritive solutions, chow, or a high-fat diet. Notably, PRLH neuron activity during oral ingestion did not increase with cumulative food intake, highlighting differences from intragastric infusions. The study designed an experiment blocking gastrointestinal (GI) signals during oral ingestion, revealing insights into the dispensability of certain feedback mechanisms during normal oral meals.
PRLH neurons displayed rapid activation during self-paced oral consumption, correlating strongly with intake in the preceding 10 seconds. These neurons responded to the taste and chemical properties of food, demonstrating time-locked activation during licking and sensitivity to caloric and sweet tastes. Taste-blind mice lacking the Trpm5 gene showed reduced PRLH neuron responses to sweet substances, emphasizing the essential role of taste signaling. Single-cell recordings unveiled that PRLH neurons integrate taste and visceral signals in regulating feeding behavior.
The study also revealed that manipulating PRLH neuron activity during licking using closed-loop optogenetics reduced food intake, primarily by influencing the size of ingestion bursts. On the other hand, GCG neurons, a distinct cell type in the cNTS, responded to GI feedback over longer timescales, influencing both ongoing consumption and the initiation of later bouts.
Continuous optogenetic stimulation of GCG neurons was found to inhibit the consumption of solid and liquid food, exerting an influence on both ongoing consumption and subsequent bouts. In contrast to PRLH neurons, GCG neuron activity was not time-locked to ingestion bouts, suggesting a role in longer-term regulation. Pre-stimulation of GCG neurons led to a sustained reduction in subsequent food intake, emphasizing their involvement in prolonged satiety. The findings underscore the distinct roles of PRLH and GCG neurons in the cNTS in orchestrating feeding regulation on short and long timescales, respectively.
The experimental protocols adhered to ethical guidelines, and the study utilized various mouse strains, including transgenic and knockout lines. Intracranial surgeries, optogenetic experiments, and behavioral assays were conducted, ensuring rigorous research practices. This groundbreaking research not only uncovers critical insights into the neural mechanisms governing meal termination and satiety but also emphasizes the brainstem’s vital role in appetite regulation.
Author: Farahnaz Mammadbayli
Editor: Elif Duymaz
Reference: Ly, T., Oh, J. Y., Sivakumar, N., Shehata, S., La Santa Medina, N., Huang, H., Liu, Z., Fang, W., Barnes, C., Dundar, N., Jarvie, B. C., Ravi, A., Barnhill, O., Li, C., Lee, G., Choi, J., Jang, H., & Knight, Z. A. (2023, November 22). Sequential appetite suppression by oral and visceral feedback to the brainstem. Nature. https://doi.org/10.1038/s41586-023-06758-2
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