Title: How does adolescent obesity change the control of dietary decision-making?
Funder: The Academy of Medical Sciences

Abstract: Obesity alters processes regulating dietary decision-making such as response to food-associated cues. Such processes are highly dependent of the prefrontal cortex. Interestingly these circuits end up their maturation during adolescence, making teens potentially more vulnerable to long-lasting impact of obesogenic diets. In this project we will elucidate how adolescence and adult obesity differentially impact cue-induced feeding and alter the functioning of prefrontal circuits. Preliminary data show that palatable foods during adolescence increases intake of obesogenic diet at adulthood and the food reactivity of the prefrontal cortex. To answer our question, we will first use fluorescent tagging of activated neurons in obese and lean mice in response to the presentation of food cues. We will the use fluorescent sensors and in vivo recordings to measure responses of prefrontal circuits in behaving animals using fibre photometry. These two approaches enable us to correlate changes in cue-induced feeding with alterations in prefrontal cortex activity. In a second part, we will use optogenetic approaches to demonstrate the causal link between changes in prefrontal activity and increased cue-induced feeding by either restoring normal feeding in obese animals or mimicking obese behaviour in lean animals. Understanding brain mechanisms underlying obesity and dysregulation of cognitive control of feeding is essential to develop novel behavioural and interventional strategies tackling this major health issue. This project will also highlight adolescence as a critical vulnerability window for the impact of dietary habits, demonstrating the need for an in-depth knowledge of the brain maturation during the postnatal life.

Lay abstract: Obesity is a major health challenge for the 21st century and is associated with several metabolic (e.g. cardiovascular disorders, diabetes…) and psychiatric comorbidities (e.g. depression). The main driver of obesity is unhealthy dietary habits with the overconsumption of food enriched in fat and sugar. Food-related stimuli like sights/smells of food or food adverts can bias food choice and trigger craving and eating. This mechanism may be exacerbated in obesity, making it harder to maintain a healthy diet. Recently, the prevalence of obesity has risen amongst teens, which is really concerning as adolescence is a crucial period for brain development. The prefrontal cortex, which plays a central role in the regulation of the response to food stimuli, is one of the last brain regions to develop. It is imperative to understand how these brain circuits may be more vulnerable to unhealthy food during development to tackle juvenile obesity. Using advanced genetic tools, we will measure ex vivo and in vivo how obesity in adolescents changes the response of prefrontal cortex to food-related stimuli. We will also selectively manipulate the activity of these brain circuits to determine the causal link between changes in prefrontal cortex response and changes in feeding induced by food stimuli in obese animals. The project aims to highlight the vulnerability of the adolescent brain to unhealthy dietary habits, but also to lead to the development of novel behavioural and interventional strategies targeting the deleterious impact of adolescent obesity on the brain and on cognitive functions.

Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE