Feeling pressure to avoid eating.
In a world where the pressure to eat or not to eat can be overwhelming, a groundbreaking study published in Nature Metabolism sheds light on the intricate mechanisms behind feeding behavior. Led by Choi Sang Daniel Lam and M. Maya Kaelberer, the research unravels a fascinating connection between stomach stretch activation of PIEZO1 on X/A-like cells and the reduction of ghrelin production and secretion, ultimately leading to decreased food intake.
Picture this: your stomach, the primary collector of the food we eat, not only senses nutrients but also informs us about the volume of food consumed. When the stomach is empty, the need for food arises; when it's full, eating should come to a halt. This delicate balance is regulated by various hormonal signals, with ghrelin playing a crucial role in signaling hunger. However, the precise sensory signals in the stomach that trigger ghrelin release have remained a mystery—until now.
The study's findings reveal that stomach stretch activation of PIEZO1 on X/A-like cells inhibits ghrelin release, curbing food intake. By genetically manipulating PIEZO1 in these cells, the researchers demonstrated a direct link between PIEZO1 activity and ghrelin signaling. Knocking out PIEZO1 in X/A-like cells led to overeating and weight gain, a phenomenon reversed by a ghrelin receptor antagonist. This highlights the critical role of PIEZO1 in regulating ghrelin and, consequently, feeding behavior.
Moreover, the study delves into the intracellular pathway downstream of PIEZO1 activation, uncovering the involvement of the CaMKKII–CaMKIV pathway in ghrelin regulation. Further experiments showed that PIEZO1 activation through an agonist or overexpression led to decreased ghrelin production, emphasizing the potential of targeting PIEZO1 for weight management.
Interestingly, the researchers also explored the impact of mechanical stretch on PIEZO1 activation, revealing that gastric stretch alone could reduce ghrelin release, independent of nutrient presence. This finding opens new doors for potential weight-loss interventions, with PIEZO1 emerging as a promising target in combating obesity.
Intriguingly, the study even touches on the translational potential for humans, showcasing a decrease in PIEZO1 expression in individuals with obesity and its recovery post-gastric bypass surgery. This suggests a novel avenue for obesity treatment through PIEZO1 modulation.
As we navigate the complex realm of hunger and satiety, the discovery of PIEZO1's pivotal role in regulating food intake offers a fresh perspective on combating obesity and promoting healthy eating habits. So, the next time you ponder whether 'to eat or not to eat,' remember to listen to your gastric PIEZO1—it might just have the answer you need.
Source: https://www.nature.com/articles/s42255-024-01002-1
Picture this: your stomach, the primary collector of the food we eat, not only senses nutrients but also informs us about the volume of food consumed. When the stomach is empty, the need for food arises; when it's full, eating should come to a halt. This delicate balance is regulated by various hormonal signals, with ghrelin playing a crucial role in signaling hunger. However, the precise sensory signals in the stomach that trigger ghrelin release have remained a mystery—until now.
The study's findings reveal that stomach stretch activation of PIEZO1 on X/A-like cells inhibits ghrelin release, curbing food intake. By genetically manipulating PIEZO1 in these cells, the researchers demonstrated a direct link between PIEZO1 activity and ghrelin signaling. Knocking out PIEZO1 in X/A-like cells led to overeating and weight gain, a phenomenon reversed by a ghrelin receptor antagonist. This highlights the critical role of PIEZO1 in regulating ghrelin and, consequently, feeding behavior.
Moreover, the study delves into the intracellular pathway downstream of PIEZO1 activation, uncovering the involvement of the CaMKKII–CaMKIV pathway in ghrelin regulation. Further experiments showed that PIEZO1 activation through an agonist or overexpression led to decreased ghrelin production, emphasizing the potential of targeting PIEZO1 for weight management.
Interestingly, the researchers also explored the impact of mechanical stretch on PIEZO1 activation, revealing that gastric stretch alone could reduce ghrelin release, independent of nutrient presence. This finding opens new doors for potential weight-loss interventions, with PIEZO1 emerging as a promising target in combating obesity.
Intriguingly, the study even touches on the translational potential for humans, showcasing a decrease in PIEZO1 expression in individuals with obesity and its recovery post-gastric bypass surgery. This suggests a novel avenue for obesity treatment through PIEZO1 modulation.
As we navigate the complex realm of hunger and satiety, the discovery of PIEZO1's pivotal role in regulating food intake offers a fresh perspective on combating obesity and promoting healthy eating habits. So, the next time you ponder whether 'to eat or not to eat,' remember to listen to your gastric PIEZO1—it might just have the answer you need.
Source: https://www.nature.com/articles/s42255-024-01002-1
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