As an important factor in human survival, the neuromodulation of feeding behaviour is an important area of research today. Eating behaviors and other lifestyle habits play an important role in optimizing health and obesity control. Feeding behavior is controlled through physiological processes related to energy and nutrient requirements, and different brain nuclei are involved in the neuromodulation of eating behavior, and understanding the function of these nuclei can help develop eating control methods. Among the important nuclei, there are not many studies on the central amygdala (CeA) nucleus and feeding behavior. CeA, one of the key brain regions that plays an important role in various physiological and behavioral responses such as emotional states, reward processing, energy balance, and eating behavior, contains γ-aminobutyric acid neurons, and it is also the main output region of the amygdala complex. In addition, CeA is also involved in a variety of molecular and biochemical factors and has extensive links with other brain nuclei and their neurotransmitters, highlighting its role in feeding behavior.
Timely energy intake is essential for organisms to survive, and appetite drives individuals to seek out and eat safe food. Appetite is positive when you are hungry and you can avoid a lack of energy in your body. However, when enough food has been consumed, the appetite cannot be stopped in time, and continuing to encourage eating will damage the digestive and metabolic systems.
Therefore, we secrete some anorexic hormones to suppress appetite, in addition to the amygdala inside the brain is also responsible for regulating appetite, suppressing the urge to eat, and reducing damage. However, when we simply recall scenes from our lives, we will find that loss of appetite does not occur only after we have eaten enough. High work pressure, poor mood or nausea caused by motion sickness and seasickness can also greatly suppress appetite, and "no appetite" has become the most direct reaction.
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According to a recent study in the journal Cell Reports, appetite loss due to stress and nausea is regulated by completely different neural mechanisms, unlike satiety. The research team discovered a new class of neurons in the central amygdala (CeA) to mediate loss of appetite caused by stress and nausea.
Previous studies have found that CeAPkcδ, a neuron located in CeA, responds to satiety signals, which in turn inhibits an individual's eating behavior. But when the downstream signaling of CeAPkcδ was examined, the scientists found that it "missed" many brain regions involved in appetite suppression, such as the lateral hypothalamus and parabrachial nucleus. This suggests that there may be other neurons that regulate the appetite suppression process.
▲Schematic diagram of the study (Image source: Reference [1])
In the new study, researchers at the Max Planck Institute for Biointelligence re-analyzed the RNA sequencing data collection of CeA, and found a class of neurons that highly express the Dlk1 protein, CeADlk1 is related to CeAPkcδ according to cell genotype analysis, but has unique gene expression characteristics, and CeADlk1 has little spatial overlap with other CeA cells, all of which support CeADlk1 as a separate class of neurons.
However, if you want to know their function, you still need to verify it through mouse experiments. The authors tried a variety of methods to induce appetite suppression, such as mimicking satiety with cholecystokinin, nausea caused by lithium chloride, and growth differentiation factor 15 (GDF15) causing internal organ discomfort. They found that CeADlk1 was only activated during times of nausea and visceral discomfort, but did not respond to feelings of fullness. In addition, quinine reagent with a bitter taste also activates CeADlk1 when it reduces the urge to eat.
▲Schematic diagram of the study (Image source: Reference [1])
Subsequently, in another mouse experiment, the researchers selectively activated CeADlk1 in some mice by optogenetic means. Compared to the control group, the activated mice approached food less often, while their total exposure time to food during the observation period was also significantly reduced, and their water intake was also reduced, and the mice rarely chose to consume food even when they were starving. At the same time, there was no difference in the amount of activity between the two groups of mice. In addition, activation of CeADlk1 did not cause anxious behavior in mice, but it did induce aversion in mice, which was mainly reflected in the reduction of social time.
The authors note that, unlike CeAPkcδ activation that primarily affects the amygdala region, CeADlk1 transmits signals to the more distant parabrachial nucleus. It can be seen that "being too full to eat" and "nausea and no appetite" are mediated by completely different neural circuits. These results will help to understand some of the diseases that cause eating behavior disorders and develop targeted treatment strategies.
Resources:
[1] Wenyu Ding et al, Nausea-induced suppression of feeding is mediated by central amygdala Dlk1-expressing neurons, Cell Reports (2024). DOI: 10.1016/j.celrep.2024.113990