Trust your "gut": "Fake sugar" can fool the taste buds, but not the "gut"...

"Your honey, my arsenic"
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Due to a series of adverse health consequences such as obesity caused by high-sugar diets, more and more people are turning to zero-calorie artificial sweeteners (sugar substitutes)
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Will this satisfy a craving for "dessert"? For taste buds, natural sugar (real sugar) is almost the same as sugar substitute, which is sweet anyway
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However, the brain can't eat this set, the real (sugar) can't be fake! Shortly after discovering sweet taste receptors in the mouths of mice 20 years ago, scientists attempted to create "sweet-sweet mice" by knocking them out
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However, they were surprised to find that even without the sense of taste, animals were still able to identify natural sugars among various sugars
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Subsequent studies confirmed that oral sweeteners were not a necessary factor in perceived sugar intake
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Many studies in the past have found that in the face of various types of sugars, both humans and animals show a preference for natural sugars
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Why is this? On January 14, Beijing time, in a new study published in the top journal "Nature Neuroscience" (IF=24.
884) in the field of neuroscience, a research team led by Diego Bohórquez, associate professor of neurobiology at Duke University School of Medicine, found that, The answer lies in the gut.
To be precise, this sensing comes from a special type of cell in the duodenum
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Because enterocytes can communicate directly with the brain via the "brain-gut axis", it alters our eating behavior
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Therefore, the research promises to lead to entirely new ways of treating the disease
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Two years ago, Bohórquez's team published a review article in the Annual Review of Neuroscience describing the special cells called neuropods
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It is a type of intestinal sensory epithelial cells that form synapses
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Originally known as enteroendocrine cells due to their ability to secrete hormones, specialized neuropod cells can communicate with neurons through rapid synaptic connections and are distributed throughout the lining of the upper intestine
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In addition to producing relatively slow-acting hormonal signals, these cells also produce fast-acting neurotransmitter signals that can reach the vagus nerve and then the brain within milliseconds
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The researchers found that injecting sugar directly into the small intestine or colon did not have the same effect
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Therefore, this sensory cell is located upstream of the gut, in the duodenum
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The latest findings further suggest that neuropod cells are the sensory cells of the nervous system, like the taste buds on the tongue that help us taste flavors, or the retinal cone cells in the eyes that help us identify colors
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Neuropod cells sense the difference between natural sugars and sweeteners, then they release different neurotransmitters into different cells of the vagus nerve, and eventually, the animal will know "this is sugar" or "this is sweetener
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In the new study, the researchers used mouse and laboratory-grown intestinal organoids derived from human cells to represent the small intestine and duodenum (upper intestine)
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Experiments have shown that real sugar stimulates individual neuropod cells to release glutamate as a neurotransmitter; sugar substitute triggers the release of another neurotransmitter, ATP
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Then, using optogenetics, the researchers could control neuropod cells in the mouse gut to turn "on" and "off" to test whether the animals' preference for real sugars was driven by gut signals
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A key technique for the optogenetics work was developed by MIT scientists, a new type of flexible waveguide fiber that can deliver light throughout the gut of a living animal to trigger a genetic response that silences neuropod cells
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The researchers found that when the animals' neuropod cells were turned off, they no longer showed a clear preference for real sugars
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This confirms that the mouse preference for sucrose is dependent on glutamatergic signaling from neuropod cells
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"Our trust in food comes from the gut," Bohórquez said.
"The
gut
knows that real sugar is what makes it both sweet and nutritious
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So the saying 'trust your gut' makes a lot of sense
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Why artificial sweeteners can't Suppressing sugar cravings, this research gives us a better understanding of that
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We can start with the gut to change the behavior of mice, which holds great promise for new therapies that target the gut
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" In future work, Bohórquez said, his team will also uncover how neuropod cells recognize other macronutrients
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Paper link: https:// https://doi.
org/10.
1146/annurev-neuro-091619-022657