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Why do we eat? Out of necessity, but also for pleasure. In the brain, two main systems control food intake: the homeostatic system, responsible for maintaining the body's energy balance so that it can function, and the hedonic system, linked to pleasure. Usually, these two systems work together: food seems more appetising when we are hungry. However, this balance can be disturbed. The reward system mechanisms involved in overeating are the same as those involved in addiction. Overeating then becomes compulsive. One of the main culprits is the particularly explosive mix of fat and sugar.

"An experiment with mice showed that when offered fatty or sugary foods, they tended to eat 30% more calories than they normally would," explains Christian Lüscher, Professor in the Department of Basic Neuroscience and Director of the Synapsy Centre for Neuroscience Research on Mental Health at the Faculty of Medicine. "But when you combine the two, their calorie consumption explodes to 250% of their natural needs. And what is true for mice is also true for humans, a fact well understood by the food industry."

Genetic predispositions exist, but remain rare

Thousands of genes seem to predispose people to obesity. "It can even be the mutation of a single gene, for example the one that codes for leptin, the hormone regulating appetite," says Valérie Schwitzgebel, Professor in the Department of Paediatrics, Gynaecology and Obstetrics at the Faculty of Medicine and Head of the Paediatric Endocrinology and Diabetology Unit at the HUG. "These children are simply hungry all the time, regardless of their food intake, which leads them to obesity from their first year of life. A mutation in the MC4R gene, which regulates appetite and energy expenditure, can also lead to monogenic obesity. Although studying these mutations can help patients and improve our understanding of the metabolic mechanisms involved, they are still extremely rare. It is much more common for obesity to have a polygenic basis - hundreds of genes are involved - which, combined with to lifestyle changes, can trigger obesity."

In her practice at HUG, Valérie Schwitzgebel has witnessed a worrying increase in childhood obesity and increasigly younger people with type 2 diabetes. "What happened in the United States a decade ago is happening in Europe. And in a few years, at least four countries will have a majority of obese people: Saudi Arabia, the USA, Turkey and Jordan. This shows that is not a disease reserved for rich countries, but one linked to profound changes in lifestyle and an overabundance of highly processed industrial foods.

Acting on several fronts

For physicians, the key to effective treatment is first to assess the patient and their environment to identify any genetic basis, but above all to understand lifestyle habits, psychological dimensions and material constraints.

"Changing a single element is not enough. The person as a whole must be taken into account," emphasises Valérie Schwitzgebel. "The whole system should be change, which includes, for example, nutritional and behavioural education, the resumption of physical activity, or even the use of medication to speed up the process. We are typically in a context where medical tailoring is essential.

The cultural and social aspect of eating remains essential: re-learning to share meals and limit food intake to mealtimes - a habit that is losing ground in many countries - is therefore the first step in the fight against obesity. Other seemingly simple but very effective measures are also important: avoiding sugary drinks, paying attention to what you eat, if possible without screens, and getting back to physical activity, which will not make you lose weight but will strengthen your body and muscles.

In addition to medical efforts, specialists are also calling for public health measures. Labelling sugary drinks to highlight their dangers, as with cigarettes or alcohol, a measure for which initial tests seem conclusive, promoting less obesogenic architecture and urban planning by building easily accessible staircases or favouring soft mobility. "Unfortunately, prevention is always poorly considered in public policy, which also goes against certain industrial interests," adds Christian Lüscher.

GLP-1 analogues could be a game changer

Has the treatment of obesity changed radically since the introduction of  'GLP-1 agonist' drugs? "These drugs are very effective and are being prescribed to younger and younger patients," points out Valérie Schwitzgebel. "However, as soon as they stop taking them, people regain weight unless they continue to change their diet and lifestyle. Their effect is therefore only transient."

These drugs act mainly on the homeostatic system by reducing appetite. But do they also affect the reward system? "A research project is underway," says Christian Lüscher. "It would indeed be interesting to better understand the brain mechanisms triggered by this drug, that has already changed the lives of millions of obese people."

Pr Christian LÜSCHER
Department of Basic Neuroscience & Synapsy Centre for Neuroscience Research in Mental Health

Pre Valérie SCHWITZGEBEL
Department of Paediatrics, Gynaecology and Obstetrics & Paediatric Endocrinology and Diabetology Unit, HUG