Behind the window of a bakery shop, lemon pies, chocolate mousses and other sweets whet the appetite. Creamy, crunchy, or soft, to dig your teeth in or to melt in your mouth, delicately flavored, or with strong or sour flavors, – all of this excites the salivary glands. It is difficult to resist a piece, and it is even harder to stop after the first spoonful. Gluttony? Neuroscientists have another name for this: dopaminergic reward system. The taste of a sugary flavor on the tongue leads the brain to produce dopamine, the neurotransmitter that stimulates the neurons responsible for pleasure. This mechanism led to the belief that the sense of taste was the main driver of sugar consumption; but neuroscientist Ivan de Araújo discovered that the body’s absorption of calories also stimulates the reward mechanism. The results of his findings, published in the March issue of the science journal Neuron, might help understand how the attraction to sweets is the source of many obesity-related problems.
Araújo, who works at Yale University’s John B. Pierce Laboratory, believes that the sense of taste, a tool to find calorific food in nature, helps animals survive. But he wanted to acquire a better understanding of the mechanism that leads to this preference for calories. This is why he delved deeper into this subject during his post-doctorate studies at Duke University in the United States, where Sidney Simon and Brazil’s Miguel Nicolelis had combined their knowledge on how cells detect taste on the tongue with detailed technical registers of brain activity that tracks the activity of groups of neurons in real time. The two researchers created a line of research that seeks to unveil the connections between the tongue’s taste buds and the brain – the neurophysiology of tasting.
In association with this team, Araújo organized an experiment using genetically modified mice that do not produce the protein required to taste sweet or bitter flavors or amino acids. He noticed that if the mice were allowed to choose to drink pure water or water with sucrose, normal mice preferred the sweetened water. It didn’t make any difference to the genetically modified mice. Then the researcher gave the modified mice more time so that they could use the metabolic effects to evaluate each of the liquids. On alternate days, he would place a bottle with clear water on one side of the cage or a bottle with sweetened water on the other side of the cage. By offering the liquid at separate times, the mouse had enough time to absorb – or not – the sugar and feel its effects. The result became apparent in the behavior: when the researcher placed the bottle of water on both sides of the cage at the same time, the modified mice quickly ran to the side of the cage where on previous days they had found the sweetened water. The mice had learned to associate the location of the bottle with the energy content of the liquid.
“It is clear that the reward the mice are looking for is not taste – it’s the calories,” Araújo concludes. To leave no room for doubt, he repeated the experiment with new mice. This time, he used sucralose, a sweetener whose taste is similar to that of sugar, but that is not absorbed by the intestine. Again, the mice with the virgin taste buds chose the sweetened water. However, as the product is not absorbed by the organism, the modified mice could no longer rely on the metabolic path to detect the sugar and did not develop any special preference for either side of the cage.
To investigate the mechanism underlying this behavior, the group measured the chemical content of dopamine in their brains. They found that in the normal mice the quantity of dopamine in the brain increased both in response to the water with sucrose and to the water without sucrose, but the genetically modified mice only reacted to the sucrose. In Araújo’s opinion, the results prove that two independent pathways drive the reward mechanism: the gustatory pathway and the metabolic one.
Sweeteners attach themselves to the receptors in the tongue cells in the same way as sugar does, and thus mislead the body. But not for very long. A study conducted by American researchers, published this year, showed that foods with sweeteners actually lead animals to take in more calories in the long term. “It is likely that the temporary profile of the dopamine released in the two pathways is different,” explains Araújo. The taste mechanism provokes an instant production of dopamine, but the researcher believes that this stimulation only lasts for a few seconds. The effect of the metabolic pathway, however, which depends on the absorption of sugar by the body, may last for a few minutes or even a few hours. This is why it provokes a more sustained production of dopamine. “It looks like the metabolic pathway has a cumulative effect that the tasting pathway lacks,” speculates the neuroscientist, who emphasizes that it is important to conduct more studies by using more accurate technology to measure the concentrations of dopamine over time.
When an animal consumes sucrose, the body produces insulin, an essential hormone for the processing of sugars. This insulin is transported to the brain and there it potentially stimulates the dopamine neurons. The resulting dopamine activates a number of brain circuits that affect the emotions. Araújo does not yet know in detail how this pathway, which starts with the body detecting calories, actually acts on the brain.
The difficulty of tracing the pathway of taste is not a problem for the researcher. Quite the contrary – he seems to prefer intricate pathways. With a degree in philosophy, Araújo became attracted by logic and decided to get a master’s degree in mathematics. Still interested in logic, he got involved in virtual neural networks during a master’s degree program in the field of artificial intelligence and robotics. Finally, he concluded that real neuron networks are more interesting, and so he decided to do a PhD in the neurophysiology of eating behavior. Now he wants to map the connections between the neurons linked to taste and those which drive people to eat.
Looking for partners, Araújo held a seminar at the Institute of Biomedical Sciences of the University of São Paulo (ICB-USP), where he met neuroanatomist Sara Shammah-Lagnado. She showed him the results of the anatomic exploration of the region of the brain that recognizes calorific foods. In an article to be published in Neuroscience this year, Sara and her team showed interconnections between one part of the brain linked to motivation and another part linked to motor reactions. “It’s an interface between motivation and action,” says the researcher.
The chance meeting between research groups led to a multidisciplinary effort. Araújo hopes he will soon have a detailed map of the brain circuits involved in the signaling pathway between insulin and the reward system, between seeing a piece of chocolate and eating it. “We see the anatomic relationships but we cannot attribute any functions to them,” says Sara, “and Ivan conducts functional experiments that allow us to test hypotheses based on neural circuits.” Thanks to this integrated approach, the team from USP hopes to specify exactly in which parts of the brain Araújo should measure the concentration of dopamine after a mouse ingests calories.
Preliminary data obtained by Sara’s group indicates that they are looking in the right place to find the relationship between eating and feeling good. “This is a line of research that will yield results,” she points out. It is a search for the home of gluttony which, prior to being a vice, ensured the survival and the proliferation of animal life on our planet.Republish