Research Summary: Adolescent mice consuming high-fat junk food till young adulthood have disrupted brain connections, causing memory loss. Remarkably, only four weeks of restricted access to the same food completely reversed all changes.
Author interview: Prabahan Chakraborty is currently a Research Assistant Professor at Dept. of Genetic Engineering, SRM IST, studying brain circuits of social behaviours. This work was done during his postdoctoral tenure.
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Lab: Prof. Freddy Jeanneteau, University: Institute of Functional Genomics, CNRS, Inserm, Montpellier, France
What was the core problem you aimed to solve with this research?
Obesity is growing worldwide, and this is particularly worrisome in junk-food consuming children and adolescents. Obese students perform poorly in cognitive tasks than their peers, needing identification of an effective therapy that can prevent such damaging effects. Previous studies have linked fasting to improved cognitive performance in adult samples. But no study has yet established a link between fasting and memory capacity during the transition from childhood to adolescence and adulthood. Our study therefore aims to lift the veil on this lack of knowledge, especially as there is an explosion in the number of children and adolescents who use social networks late at night, pushing back mealtimes and leading to overconsumption of junk food. We wanted to first, understand the neurobiological bases of such cognitive decline and second, devise a strategy with strong translational potential that can reverse these effects.
How did you go about solving this problem?
We used a mouse model to address this problem, where male and female juvenile mice got unrestricted access to high-fat diets early in life, continuing till they became young adults. Over a 14-week long experimental period, we combined behavioral analyses to test memory along with transgenic tools (knock-in mice), longitudinal imaging techniques (in vivo 2-photon microscopy), intersectional genetic strategies (chemogenetics) and pharmacology. We observed a shift of the feeding cycle, and so as a therapeutic intervention, we implemented time-restricted feeding – since limiting access to the same high-fat diet may have a better translational potential for adolescent subjects than alternate strategies like strict caloric restriction. Overall, this study involved long-term brain implants in mice (hippocampal windows), virus mediated expression of transgenes, state-of-the-art techniques to identify memory-maps, and longitudinal analyses of behavior over time in the same animals before and during high-fat diet, as well as after intervention with time-restricted feeding.
Eat your burgers but respect your circadian rhythms. They organize hormonal responses in the brain and body that control your memory traces.
How would you explain your research outcomes (Key findings) to the non-scientific community?
Not just what we eat, but when we eat also has a huge impact on health. Eating junk food affects your body and brain. Importantly, munching food rich in calories and fat throughout the day, coupled with eating such food at misaligned meal timings, rewires the connection between neurons in your brain. As a result, memory is stored inefficiently, causing cognitive loss and poorer performance in tasks. The crucial period between adolescence and adulthood is particularly sensitive to these effects. However, you can reverse this by correcting your meal timings and restricting when you eat the same high-fat food. Extrapolating our observations in mice, a few weeks of restricted access to such food during only the active hours of the day can correctly rewire the brain and improve your cognition in individuals who would have been consuming the same diet at liberty in the past. We note that these results need to be validated in humans before they can be used to inform health advice and school policy.
What are the potential implications of your findings for the field and society?
This is the first study that has longitudinally imaged synaptic connections in the changing brain in mice feeding an obesogenic diet. It is also a key study to have evaluated long-term consequences of a high-fat diet consumed early in adolescence, on memory and memory-related biological processes. Importantly, a key corrective role of time-restricted feeding has been proven at multiple biological scales (behavior, circuits, signaling). Together, observations from this study – validated with follow-up studies in human subjects – could inform policymakers and agents of social change in the future to enforce stricter guidelines on fast food marketing and consumption, particularly in children, adolescents, and young adults.
What was the exciting moment during your research?
One of the key moments that took my breath away was when I visualized the connection between neurons in the brain of a living mouse for the first time. What was even more amazing was witnessing dynamic changes in the same connections over time, as we repeatedly imaged the same section of the neuronal branch over the following days and weeks.
Paper reference: Chakraborty, Prabahan, Yann Dromard, Emilie M. André, Maheva Dedin, Margarita Arango-Lievano, Ana Raner, Antoine Besnard et al. “Meal scheduling corrects obesogenic diet induced-uncoupling of cortico-hippocampal activities supporting memory.” EBioMedicine 117 (2025). https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00227-0/fulltext
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