Researchers discover a new gut-to-brain sugar pathway.
The sugar epidemic in America has reached deadly proportions with the average person’s intake of this substance now averaging more than 100 pounds annually. Sugar addiction has been linked to obesity-related conditions such as diabetes, affecting more than 500 million people globally. Sugar and artificial sweeteners are known to trigger specialized taste buds on the tongue to activate pathways in the brain, implicated in sugar cravings.
Animals, however, can develop a strong preference for sugar even without these specialized sweet taste receptors, indicating an unknown mechanism of sugar addiction in the body independent of taste, promising answers regarding a host of chronic diseases where sugar is implicated in the pathology.
Sugar registered by gut-brain axis
Now, a study from researchers led by HHMI identifies a population of neurons in the vagus nerve and brain stem activated by sugar when it enters the gut, independent of the tongue’s taste receptors. The team states this specialized gut-brain circuit is not activated by sweeteners, possibly explaining why some sugar substitutes never seem to be able to satisfy sugar cravings. The study is published in the journal Nature.
Recent studies from the team have demonstrated sugar and artificial sweeteners switch on the same taste-sensing system contained on the surface of the tongue linking to the brain’s gustation and reward centers. Once in the mouth, sugar and its’ substitutes turn-on the same sweet-taste receptors on taste buds, initiating signals transmitted to the part of the gustatory cortex in the brain that processes sweetness.
The gustatory center also links to the brain’s reward center to ingrain preference, with the hyperactivation of this brain region shown to cause addiction. However, when these sweet taste receptors are deleted in mice they still crave sugar, leading the group to hypothesize the existence of another sweet-activated pathway to the brain. The current study demonstrates how a population of neurons in the vagus nerve and brain stem are activated via the gut-brain axis to create a preference for sugar.
Eliminating sugar cravings
The current study focuses on a brain area called the caudal nucleus of the solitary tract, or cNST, located in the brain stem, as it is activated when sugar is delivered directly to the gut of mice bypassing sweet taste receptors on their tongues.
The lab then recorded brain-cell activity in the vagus nerve, an established pathway linking the brain and the body’s internal organs, under the same conditions. Results identify a cluster of cells in the vagal ganglia, masses of nerve tissue in the vagus responsible for transmitting sensory impulses, that respond to sugar delivered directly to the gut in mice, information it then passes along to the cNST.
Data findings show inhibiting a sugar-transporting protein known as SGLT-1 in the gut eliminates the animals’ neural response to sugar, suggesting SGLT-1 alerts the brain to the presence of sugar in the gut; thus mapping the final part of the gut-to-brain sugar circuit.
Results show silencing this gut-brain circuit completely eradicates the animals’ craving and preference for sugar, illustrating how the modification of this circuit impacts the animal’s need for sugar. Data findings show when the cells of the vagal ganglia are stimulated every time the animal consumed a sugar-free Kool-Aid drink, the mice act as if they are ingesting real sugar, essentially controlling the brain to believe and act as if it is receiving the real thing.
Nextgen artificial sweeteners
The lab concludes this data could also pave the way for a new generation of sweeteners and artificial sugars, capable of tricking the brain into activating both the taste-receptor-to-brain axis and the gut-to-brain circuit to simulate the intake of real sugar.
The team surmises they identify a gut-to-brain circuit whose neurons are stimulated only by sugar delivered directly to the gut, remaining unreactive to artificial sweeteners. For the future, the researchers state their discovery holds great potential for reducing sugar cravings, and in the treatment of obesity and diabetes through the manual regulation of this gut-brain axis.
Source: Howard Hughes Medical Institute
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