Food is essential for survival but is also a source of pleasure. The release of dopamine in the so-called “reward” neural circuit is a key mechanism in the pleasure associated with food. This circuit is also the one used by so-called drugs of abuse (such as cocaine or morphine) to exercise their addictive property.
On the surface of the neurons that release or respond to dopamine, there are enzymes capable of using a form of lipids (from fatty foods) provided directly by food: triglycerides. This observation is astonishing in that the brain is considered as an organ which consumes only sugar for its energy needs. So we can consider that the triglycerides could act on these neurons not as an energetic substrate but rather as a “signal” or information and in this directly modulate the activity of dopamine neurons to modulate the motivation and pleasure associated with food for example.
When fat reaches neurons directly
In our study, we were first able to demonstrate that the triglycerides, that is to say, the lipids which are found in the blood after the digestion of fats by our intestine, are capable of reaching the regions of the brain where are the neurons that, within the “reward circuit”, respond to dopamine. In these same neurons, we show that the molecular tools necessary for the detection and use of these lipids are present. In particular, we find on the neurons which release dopamine or those which, downstream receive and respond to dopamine, an enzyme specialized in the cutting of these triglycerides into lipids simpler and easier to use by the cell: lipoprotein lipase. These results suggest that the neurons in the reward circuit would, therefore, be able to respond to triglycerides, as they do for a neurotransmitter like dopamine.
In order to test this hypothesis, we simply caused a small increase in the triglyceride levels in the blood, as a meal would do, but by directing these lipids only to the brain. So we were able to observe what consequences this elevation of lipids towards the brain can have on the activity of the neurons to dopamine on the one hand but also on behaviors which, in the man as in the animal, testify to the activity of the reward system neurons and their ability to chemically and electrically encode the facets of pleasure and desire associated with food or other substances such as psychotropics.
First, we were able to directly record the electrical activity of these neurons. This type of “electrophysiological” recording experience is very classic in the field of neuroscience and consists of implanting an electrode in a neuron to measure electrical activity. The medium spiny neurons that are found in the region of the brain called the striatum, represent one of the major populations of neurons which, thanks to a dopamine “receptor” they possess, are capable of translating a change in dopamine release into complex behavior in animals. Whether “ex vivo”, on a brain slice containing these neurons kept active, or “in vivo” using an imaging method to visualize the activity of these neurons in a free animal, we observed that the addition of lipids decreased the activity of these neurons “responders” to dopamine.
3D view of the striatum.
This first result confirmed our idea and we, therefore, hypothesized that triglycerides could, like dopamine, participate directly in the development of the pleasure and desire response associated with a stimulus. This notion is defined under the term of “reinforcer”. A positive enhancer (like the first square of chocolate in children) is a stimulus that, thanks to the release of dopamine which it causes, will be perceived as pleasant, pleasant and reproducible as quickly as possible.
In order to test whether triglycerides could act on the brain as positive enhancers, we used a place preference behavior test. Under this complicated name, the test is quite simple. A mouse is placed in a box containing two very distinct compartments which the animal is free to explore. The two compartments have a different appearance from each other (blue and green for example) which allows the mouse to differentiate them perfectly. During a few sessions, the mouse will receive a little lipid towards the brain in one compartment (blue) and saline solution in the other compartment (green).
On the day of the test, the mouse is released in the middle of the compartments with the possibility of going where it prefers. If the animal rushes towards the blue compartment which was associated with a little lipid towards the brain, this will testify that this experience was perceived as pleasant and that the animal would like to reproduce it. This is exactly what we observed and we concluded that triglycerides, when they reach the brain, can, therefore, act as a positive enhancer: a pleasant chemical signal and to reproduce if possible. At the level of a possible mechanism of action of these lipids on these neurons, we were able to demonstrate that the enzyme lipoprotein lipase, present on the surface of neurons which respond to dopamine was very important. Indeed,
Similar results in animals and humans
These results were obtained on the rodent which is a model allowing to study certain cellular and molecular mechanisms in a more precise way. However, as with sugar or proteins, the increase in lipids in the blood after a meal is a very conserved physiological phenomenon that is found in humans as in mice. So, we wanted to see if the phenomenon that we had observed in our mice could have an equivalent in humans.
In this experiment, we used functional brain imaging(in collaboration with our American colleagues at Yale University), a technology that makes it possible to visualize in humans the changes in activity in defined areas of the brain. What we tested is the way the brain responds to the smell of food (in this case strawberry or chocolate cookie), whether we are fasting or just after a meal. As you would expect, the smell of a strawberry or chocolate cookie when hungry causes activation of the reward zones and this response is attenuated when one has just eaten. By looking at the blood parameters which are directly modified by a meal (sugars, insulin or triglycerides) we observed that the activity of the prefrontal cortex (one of the regions of the reward circuit which makes the link between the smell of food), its taste and the pleasure it causes were directly and specifically correlated with the increase in triglycerides circulating in the blood after a meal. This result is important since it allows us to consider that in humans, as in the trimmer, the circulating triglycerides could act “directly” on the areas of the brain involved in the “reward” associated with food.
As a whole, this work, therefore, makes it possible to highlight, for the first time, that the lipids that are found in the circulation after the digestion of a meal, can act directly on the neurons of the “reward system to the dopamine ”and thereby modulate the components of desire and pleasure associated with food. Our next studies will try to understand if this mechanism of detection of lipids by the neurons of the reward system, can prove to be deficient in certain cases and lead to appetite disorders or loss of satisfaction associated with food. Indeed, the concentrations of circulating triglycerides vary according to the meals. But when these meals are too rich and too frequent or in conditions of significant overweight (obesity),
It is with this in mind that our study offers new insights that potentially explain why the access and consumption of rich foods can contribute, by disrupting the reward system, to the establishment of compulsive eating behaviors and promote development. obesity.