Flavor alchemy

Calories give us pleasure. That seems obvious: ice-cream, french fries, spring rolls, or halva are all in the yum category. But there is pleasure even if there is no flavor. This is a recent discovery that hints that great food goes beyond good flavor. It needs to have calories. How we can manage that requirement and not promote the rise of obesity is a challenge every cook needs to confront.

Mice counting calories

De Araujo and collaborators in the journal Neuron report on an experiment with mice that shows that the pleasure mechanism in the brain responds to the calories in food: more calories, bigger pleasures. The experiment has not been repeated with humans, but the food regulation systems of mammals are all so similar that the results must hold for us.

Through genetic engineering it is possible to create a mouse that cannot taste sweet. Sweet (together with umami and bitter) is perceived through molecules on the membranes of the taste buds cells, but for the signaling to work the cell also needs some ion channels. The genetically modified mouse is created by removing the chunk of genetic material that makes those helpful ion channels from the mouse’s DNA. Scientist call them knock out mice.

To be double sure the knock out mice don’t have a sweet tooth, the scientists put mice that have fasted for a day in a cage with two sipping bottles: one with water and another with sugary water. Regular mice will sip around 500 times between both bottles in a half hour session, but three time more often from the sugary water than the knock out mice with the missing sweet tooth. (No graduate students were harmed counting licks, as a lickometer was used.) The same test can be done with an artificial sweetener, sucralose (often sold as Splenda), and regular mice prefer the sweetened water and the knock out mice continue not caring.

After the scientists are convinced that the knock out mice cannot taste sweet and that the mice know how to use the sippers, they tested the bottle preferences of the mice for 4 days, switching the position of the sippers each day. The knock out mice with no sweet tooth preferred the water with sugar, but not the water with Splenda. The regular mice preferred sweet water (sugar or Splenda).

Not satisfied, de Araujo and friends went on to check the release of dopamine in the brain of the mice. Dopamine is a small molecule used in the brain to reward desirable behavior. They concentrated on the nucleus accumbens (NA) and the ventral tegmental area (VTA), two small regions in the middle shell of the mammal brain that are at the core of the reward circuit. The VTA receives information from around the brain. If things are going well, the VTA informs the NA by releasing dopamine. The NA then informs the motor control and attention focusing regions of the brain that whatever they are doing gives pleasure. For Araujo’s knock out mice, pleasure was drinking water with calories.

Flavor and calories

Araujo and collaborators observe that if a knockout mouse has never seen the cage with the two sippers it goes for either just as often. As soon as it drinks calorie-rich sugar water, its brain releases dopamine, but its choice behavior does not change in the first session. That means that the reinforcement for preferring sugar water starts immediately, but the mouse only changes its actions after some learning time. For the regular mice, the flavor was sufficient to release the dopamine and the presence of calories does not increase the amount of dopamine released.

We create associations between flavor and calories. It’s not yet clear if calories or flavor alone can do it, and cooks may be able to play with these associations. My guess is that a few days to maybe two weeks is all one needs to have the reinforcement manifest itself as behavior. Seth Roberts, once a professor of psychology at Berkeley, has authored a best-selling diet book on the associations between flavor and calories. Roberts has suggested a model of how mammals set their weight. This model is the basis for his diet and Araujo’s work just added a bit more support to it.

Besides the the six tastes (it’s six because of fat, see a previous post), we also have other sensations in our mouth. We can sense when something is spicy hot, as when food has cayenne or wasabi, and when it has a chemical coolant, such as the menthol in chewing gum. These sensations are different from tastes because they rely on little (molecular little) tubes on the nerve cells. They are not in our taste buds but in our mouth and throat. These little tubes allow certain molecules to enter the cells and change some of the chemical reactions that are going on inside. This is how we perceive spicy hot, temperature, and a few other things no one is quite sure.

These little tubes are known as TRP ion channels. They let ions and some small molecules in and out of cells. Because they are made out of proteins that look like each other, biologists have checked that the human genome codes for at least 28 different TRP ion channels. The fun part for scientists is that most of them have unknown functions. One of them, trpa1, seems to detect low temperatures (under 15ºC) but also the hotness related to mustard. Maybe there is some room for culinary experimentation with mustard or wasabi ice creams. (Exotic ice creams are now all the rage. Heston Blumenthal churned mustard ice cream early on, but I’ve never tried it.) The little ion tubes can be desensitized by certain chemicals, which opens up other culinary possibilities.

Sour and salty seem to use mainly TRP channels, but the other tastes use specialized cell membrane molecules called GPCR. The GPCR communicate to the inside of the cell the presence of some molecule on the outside. Say you have just eaten a nice piece of chocolate cake. The sucrose from the sugar will find its way to a taste bud. A taste bud has many taste receptor cells (often abbreviated TRC) and each cell will have a different collection of GPCR. Sucrose will stick only to one type of GPCR called T1R2+T1R3. The GPCR with the captured sucrose moves along the cell membrane and with the help of other molecules produces camp, which is then used to activate enzymes and start other reactions in the taste receptor cells that will signal the brain that a sucrose was inside your mouth.

We have one GPCR for sweet, one for umami, and it looks like one for fat. But we have over 30 for bitter. We cannot tell one bitter taste from another: the GPCR for bitter tend to be on the same taste receptor cell, so the brain cannot tell them apart.

Words cost so little (0.2 cents per spoken word, I estimate). But one cannot throw taste, aroma, and flavor around. Taste comes from the sensations one gets through our taste buds in our mouth. Aroma through our nose. And flavor is the combination of aroma, taste and other sensations we get from food when we eat. There are also mechanical sensations. These include the texture, the crunchiness, the slipperiness of food, what we call mouth feel.

Taste and aroma are closely related. They work by having cells in our body convert the presence of a molecule into electrical signals that our brains then interpret — fishy, floral, bitter, sweet — pick your adjective. Our sense of smell comes from this small patch of skin in upper part nasal cavity. Our nasal cavity is the hole we have above the roof of the mouth. Taste comes mainly from the tongue, but we have a few taste buds in other places inside our mouths.

Humans can identify five or six tastes and a few sensations in their mouths. The basic tastes — sweet, bitter, umami, sour, and salty — are now being joined by a sixth one: fatty. It appears that mammals have taste receptor cells for fat. This discovery was made on mice in 2005 by Philippe Besnard and friends by connecting a protein, called CD36, which exists on the surface of cells, to the wants of mice for fatty food. Humans also have the CD36 protein, and experiments at Purdue University show that humans can detect the taste of fat.

Fats can be detected through their texture, but that is not the main clue used by our bodies. Experiments show that there is another mechanism. Just by having fats in our mouths the level of triglycerides in our blood goes up. We store triglycerides and not just any fat in our bodies. If the same experiment is repeated with a fat-free butter (simulating butter’s mouth feel), the level of triglycerides is half of the level with real butter. So the oil’s texture is not enough and there has to be another mechanism for detecting fat. My money is on CD36.