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