From dish to brain, how dopamine influences our behaviour

For a long time, the brain was thought of as being the realm of glu­cose. This sug­ar mol­e­cule played the lead­ing role as the main ener­gy cur­ren­cy, fuelling neu­rons and acti­vat­ing our reward sys­tem. It was accept­ed that triglyc­erides, large lipid mol­e­cules, did not cross the blood-brain bar­ri­er. This bio­log­i­cal bar­ri­er around the brain was thought to be imper­me­able to the fats in our food that cir­cu­late in the blood. In a study pub­lished in 2020¹, Chloé Berland, Giuseppe Gan­garossa, Serge Luquet and their team debunk this the­o­ry and add an extra sur­prise: lipids may also play a role in the reward system.

“For a long time, it was believed that triglyc­erides did not enter the brain. In real­i­ty, they do, and they even act on dopamin­er­gic neu­rons,” explains Giuseppe Gan­garossa, neu­ro­bi­ol­o­gy lec­tur­er and researcher at Uni­ver­sité Paris Cité. These neu­rons, which use dopamine as a neu­ro­mod­u­la­tor, play a cen­tral role in reg­u­lat­ing behav­iours, par­tic­u­lar­ly those relat­ed to food. The direct involve­ment of triglyc­erides there­fore pro­vides new insights into cer­tain imbal­ances observed in eat­ing behaviour.

One of the first find­ings to emerge from the study relates to lipopro­tein lipase (LPL), an enzyme respon­si­ble for break­ing down triglyc­erides so that fat­ty acids can be stored in cells. This enzyme is found in neu­rons that send or receive dopamine. “LPL breaks triglyc­erides down into small­er pieces that can act as mes­sen­gers in the brain,” says Giuseppe Gan­garossa. LPL has joined the ranks of brain mes­sen­gers such as dopamine, sero­tonin and glutamate.

Anoth­er find­ing of this study is the role these lipids play in how the brain man­ages food. Let’s take a look at how dopamine – a neu­ro­mod­u­la­tor – works. It acts in the brain via sev­er­al types of recep­tors, includ­ing those of the D1 and D2 fam­i­lies. D1 recep­tors are asso­ci­at­ed with acti­va­tion mech­a­nisms, while D2 recep­tors are more close­ly linked to inhibition.

“These two voic­es rep­re­sent the “go” and “no-go” respons­es to food,” sum­maris­es Giuseppe Gan­garossa. How­ev­er, accord­ing to the researcher, triglyc­erides may specif­i­cal­ly mod­u­late the activ­i­ty of D2 neu­rons by dis­rupt­ing their acti­va­tion. “Lipids inhib­it the “stop” – or “no go” – sig­nal. It is thought that in over­weight peo­ple, D2 neu­rons become resis­tant to the lipid mes­sage when it is present in excess and no longer lis­ten to the stop sig­nal.” A neur­al path­way that has become deaf to its messenger.

But it is dif­fi­cult to focus on the role of lipids in reg­u­lat­ing the reward cir­cuit and food intake with­out tak­ing a step back. “The brain is con­stant­ly com­mu­ni­cat­ing with the rest of the body, par­tic­u­lar­ly the gut. It is not an iso­lat­ed organ; every­thing is con­nect­ed,” explains Giuseppe Gan­garossa. Here, we are par­tic­u­lar­ly inter­est­ed in inte­ro­cep­tion, i.e. the abil­i­ty to per­ceive inter­nal sig­nals (hunger, sati­ety, emo­tion­al state, etc.), and two-way com­mu­ni­ca­tion between the brain and the periphery.

To stay in touch with the rest of the body, our cen­tral ner­vous sys­tem uses, for exam­ple… lipids, again! These endoge­nous lipids – which do not come from food but are syn­the­sised by our organs – are endo­cannabi­noids, capa­ble of link­ing the periph­er­al sys­tem. This reg­u­la­to­ry sys­tem is notably involved in preg­nan­cy, pain per­cep­tion, mood, mem­o­ry, appetite and the phar­ma­co­log­i­cal effects of cannabis.

In 2022, Chloé Berland, Giuseppe Gan­garossa and the team at Uni­ver­sité Paris Cité pub­lished a study²³ link­ing these endoge­nous lipids to extreme eat­ing behav­iours. The exper­i­ment went as fol­lows⁴: lab­o­ra­to­ry mice were giv­en food that was very high in fat and sug­ar for one hour each day, in addi­tion to their usu­al diet. This short-lived treat, which allowed researchers to study food intake linked sole­ly to plea­sure, became the rodents’ favourite food, and they grad­u­al­ly devel­oped a com­pul­sive eat­ing dis­or­der: binge eat­ing, which involves con­sum­ing exces­sive amounts of food in a very short peri­od of time. Beyond the sim­ple release of dopamine in the brain, the study shows that this behav­iour may be linked to the release of endocannabinoids.

“Binge eat­ing involves a dis­rup­tion in the syn­the­sis of endoge­nous lipids, the famous endo­cannabi­noids. As a result, these periph­er­al mes­sen­gers are no longer syn­the­sised cor­rect­ly and their quan­ti­ty increas­es, which has the effect of inhibit­ing the vagus nerve,” explains the neu­ro­sci­en­tist. How­ev­er, this vagal axis is direct­ly linked to the feel­ing of satiety.

With­out this acti­va­tion, mice feel less full and con­tin­ue to eat com­pul­sive­ly. One of the ther­a­peu­tic approach­es to these extreme behav­iours would there­fore be to tar­get the endo­cannabi­noid recep­tors to dis­able them, slow­ing down the reward sys­tem and trig­ger­ing sati­ety. Lipids – like sug­ars – there­fore also appear to play a deci­sive role in dis­rupt­ing our reward cir­cuit and our food man­age­ment. This rais­es the ques­tion: could eat­ing too much sug­ar or too much fat make us addicted?

The idea of “food addic­tion” often comes up in pub­lic debate. Some symp­toms observed dur­ing sug­ar with­draw­al, such as irri­tabil­i­ty and stress, are some­times linked to those asso­ci­at­ed with psy­choac­tive sub­stances. How­ev­er, accord­ing to Giuseppe Gan­garossa, the com­par­i­son with tra­di­tion­al drugs remains lim­it­ed. “Sug­ar and fats are not ‘drugs’ like psy­chos­tim­u­lants. They act through­out the body, not just in the brain. How­ev­er, some mech­a­nisms seem com­mon between them.” Unlike addic­tions to psy­choac­tive sub­stances, which main­ly focus on neur­al sys­tems, the mech­a­nisms at work here involve sev­er­al organs, sys­tems and lev­els of reg­u­la­tion. “That’s why research on food is more com­plex and requires a much more com­pre­hen­sive, holis­tic approach,” he concludes.

Sophie Podevin