Dieting is notoriously difficult. Thanks in part to evolution, we love foods that are high in calories. Not only that, but once we have experienced the kind of high-calorie foods that surround us in the modern world, more nutritionally-balanced foods become much less attractive. But why?

To understand how the brain makes dieting so difficult, and high-calorie foods so tempting, the authors of a recent study turned to mice, where they could record and manipulate the activity of specific neurons involved in energy balance and reward. They asked how exposing mice to high-calorie foods affected their consumption of, and neural responses to, regular foods.

When researchers gave the mice access to both high-fat (HFD) and standard (SD) diets, mice completely stopped eating the SD almost immediately, and preferred the HFD. They then removed the HFD, and saw that mice still ate very little SD, and so lost substantial weight. This devaluation of regular food was so strong that even fasting mice presented with an SD ate very little — they would only eat a lot if the HFD was available. Just experiencing the HFD for 24 hours was enough time to make the SD less tasty.

To see how HFD exposure affects the brain’s response to food, the scientists recorded the activity of AgRP neurons, a population of neurons that is active during hunger and controls energy balance, and midbrain dopamine neurons, which release dopamine as a signal of reward. Exposure to the HFD greatly reduced the response of both groups of neurons to the SD: afterward, these neurons would only respond strongly to the HFD. Regular food became less rewarding, and less satiating, than high-calorie food.

Under normal conditions, AgRP neurons would only respond to food when a mouse is hungry. But after HFD withdrawal (mimicking dieting), the AgRP neurons became so sensitive to HFD that they would respond even if the mouse was not hungry. This could explain why when we diet, high-calorie foods are so hard to resist – these foods become rewarding even when we aren’t hungry.

This study suggests that exposure to a HFD alters the brain’s response to food so that only high-calorie foods are rewarding and satiating, while more nutritionally-balanced foods become less valuable. And, abstaining from high-fat foods might just make our brains' hunger centers responsive to these foods even when we’re not hungry, making it difficult to resist the urge to binge. Research on the circuits that regulate food intake will potentially lead to therapies that allow us to manipulate these biological urges and control the obesity epidemic.