Why do we overeat?

Satiation and appetite could be linked to a specific region in the brain
29 November 2021

Interview with 

Nick Betley, University of Pennsylvania


Eating Cake


Now Christmas is on the way and, as the old saying goes, “your eyes are often bigger than your stomach”. So true for many of us. But it turns out that a miscalculation in a set of nerve cells in the brain’s appetite and reward system could be what triggers overeating. Julia Ravey spoke to Nick Betley, at the University of Pennsylvania, to hear what he has in mind...

John - Because of these highly caloric, highly palatable foods, people end up eating just a little bit more food than they should every day. And by eating just a little bit more food every day for a long period of time, you put on a lot of weight. So in our study, we took advantage of the fact that there are people who have a genetic disorder known as Prader-Willi syndrome. One of the consequences is they have an insatiable appetite. We reasoned that they must be missing a neuro-signal for satiation in the brain. There must be something different about their brains from everybody else's. We compared neural activity in the brain of individuals with Prader-Willi syndrome, to individuals who don't have this syndrome. And it turns out that in control subjects, the cerebellum is activated by food chews and hunger and Prader-Willi syndrome individuals are completely missing that cue.

Julia - How did you find out what this region of the brain does?

John - The cerebellum is typically known for being involved in motor function and coordination, but never before has the cerebellum been implicated in food intake and food intake control. Based on finding the signal in Prader-Willi subjects, we transitioned our research to rodent models where we could go inside of the brain and manipulate neural activity. We found a subset of neurons in a very discreet region of the deep cerebellar nuclei, that when activated actually limit the animals meal size about 75% in that individual meal.

Julia - Did this alter the behaviour of the mice in any other way?

John - We know that the cerebellum's involved in a lot of other behaviours, specifically things like motor behaviour. So we were worried that maybe the animal wasn't eating as much because the animal wasn't moving as well. We performed a series of experiments to make sure that motor function was intact so these animals can run like a normal animal.

Julia - Where the cells are active, do you think these mice enjoyed their food as much?

John - What we found is that the cerebellum is actually interfacing with the reward system to reduce the reward value of additional consumption. This would be like you stopping eating peas and rice because you've had enough of food and you're homeostatically sated, but if your cerebellum is more active, it would reduce the reward value of even things like chocolate cake.

Julia - Do you think the cells might operate in a similar way in humans?

John - Yeah, that's what we think is so exciting about this study. We started with a human task-based FMRI study. We went into the mouse brain to identify the precise neurons, to understand every molecule in these neurons, to try to understand how they influence neural activity in other regions of the brain. But now that we've understood all that, maybe we can pull back and go back to the humans and see if activating these neurons in the human brain will actually reduce meal size. And so could you imagine if we could develop a hat with some magnets in it that you could put on before you eat your meal that reduces the size of your meal by say 25% and you just eat a little bit less every day without feeling hungry, this would be a great way to lose weight. So maybe that piece of chocolate cake at the end of your meal will be slightly less palatable, and maybe you will have a smaller piece of chocolate cake. So you'll still be able to enjoy life. You just won't eat past your homeostatic checkpoint.

Julia - Do you think these results can help change the stigma attached to obesity?

John - I think it could change the stigma attached to obesity and other neural disorders in general. I think knowing that food intake control is regulated by neural circuits in the brain and that the activity in these neurons that is independent of an individual's willpower is actually controlling or modulating how much food an individual eats, is powerful information. And so by better understanding how these circuits work, we have the potential to really change the way people think about obesity and really understand it as just another type of disease. Just as if you had a heart disease.



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