Mice seek out the calories in sweet foods even if they can't taste the sweetness.
Crave sweets? Well, stop blaming your sweet tooth. Researchers have found that mice prefer sugary water even if they lack a gene needed to taste it.
Although the mice could not taste sweets, reward centres in the brain reacted when the mice drank water spiked with sucrose, but not when they drank water mixed with a low-calorie artificial sweetener. The results, published this week in Neuron1, suggest that mice can detect calories without relying on their taste buds — a finding that could change our understanding of the sugar cravings that can plague dieters and contribute to obesity.
The presence of a calorie-sensing pathway makes evolutionary sense, says study author Ivan de Araujo, now at Yale University in New Haven, Connecticut. “The taste system evolved to allow animals to quickly detect what is worth eating versus what is not,” says de Araujo. “But the real reward that they need is not the taste itself but the calories.”
A matter of taste
Previous work has suggested that rats could also sense sugars without tasting them. Anthony Sclafani of the City University of New York and his colleagues trained rats to associate a flavour of unsweetened Kool-Aid (an artificially flavoured drink) with the infusion of either glucose or water directly into their stomachs2. If, for example, they were given grape Kool-Aid together with water, and cherry Kool-Aid together with glucose, over time the rats developed a predilection for cherry Kool-Aid when given a choice between the two.
Sclafani and his colleagues also showed that the neurotransmitter dopamine was released when animals were given the glucose/Kool-Aid mix. Dopamine has been associated with the perception of a reward, but the researchers did not know what exactly triggered the dopamine release. Sclafani says that they assumed that the taste had become associated with the glucose reward, and it was the taste that boosted dopamine levels.
The new work, however, contradicts that assumption. “Now they’ve shown that the nutrient can directly activate the brain reward system after it reaches the gastrointestinal tract,” says Sclafani.
The new study used mice that lack a protein called TRPM5, and so are unable to detect sweet or bitter tastes. “They are completely taste-blind,” says Charles Zucker, a neurobiologist at the University of California, San Diego.
Despite the taste-blindness, de Araujo and his colleagues found that over time, the mutant mice learned to favour sugar water just as much as normal mice. They did not, however, favour water sweetened with sucralose, a low-calorie artificial sweetener. This suggests that the mouse body does not learn from the taste, but rather from the calories in sugar.
“Once the animal’s metabolic system gets the reward for that sugar, he will now go back to the source of that sugar,” says Zucker, “even if he cannot detect it as being ‘sweet’.”
Some sugars seem preferable to others. Sclafani and his colleagues have shown that rats respond specifically to glucose, but responses to fructose are much weaker. Sucrose, the sugar used in de Araujo’s experiments, is broken down by the body into glucose and fructose.
At the moment the researchers can only speculate about why mice might have such preferences, or how the sugar is perceived. It is possible, says de Araujo, that the dopamine-producing systems that detect appetite-related hormones might be involved.
de Araujo, I. E. et al. Neuron advance online publication, doi:10.1016/j.neuron.2008.01.032 (2008).
Perez, C., Lucas, F., Sclafani, A. Physiol. Behav. 64, 483-492 (1998).
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Ledford, H. The appeal of sugar goes beyond taste. Nature (2008). https://doi.org/10.1038/news.2008.692