French Fries or Side Salad?

August 18, 2020

Written by: Nitsan Goldstein


If you’ve ever tried to lose weight by dieting you know that it is extremely difficult. Reducing the number of calories you consume makes you feel hungry, which is an unpleasant sensation. On top of that, you are probably also denying yourself the pleasure of eating foods you find highly rewarding, like dessert. What areas of the brain are affected by consuming foods that are high in fat or sugar, and why does eating them make it so hard to stop? New research using mice uncovers areas of the brain that may partly explain why dieting is so challenging.


Why am I always hungry?

Everyone knows that hunger is an unpleasant feeling. This negative feeling is what prevents many people from starting a diet or is the reason for abandoning a diet. Neuroscientists have tried to pinpoint where hunger is signaled in the brain and why it may cause this unpleasant feeling, or “negative affect.” From studies in rodents we know there is a small population of neurons in the hypothalamus, an area of the brain that regulates basic survival behaviors, that becomes very active during hunger. We’ll refer to them as the brain’s “hunger neurons.” These neurons are activated over time when an animal does not have access to food, and then rapidly silenced when food is available and consumed1,2.


One hypothesis was that activity in these neurons may cause the unpleasant feelings associated with hunger. Since you can’t ask a mouse how they’re feeling, scientists have to infer whether an experience is positive or negative to a mouse by testing whether or not they will avoid an environment that they associate with that particular experience. When animals learn to associate activity of the hunger neurons with certain environments, the animals avoid those environments1. This avoidance suggests that the activity in the hunger neurons does in fact promote an unpleasant, negative feeling, just like hunger in people!


Have you ever thought about what exactly relieves feelings of hunger, even before you eat enough to feel full? Let’s think about an example. Imagine you are quite hungry, and you are waiting for your food at a restaurant. The minute you see the waiter with your food you are elated, right? You haven’t eaten anything yet, but the sight of the food immediately relieves the unpleasant hunger you’ve been experiencing. Now imagine that you just got back from a week-long trip to Italy where you ate pizza, pasta, and gelato every day. If you order a salad at a restaurant on your first day back, seeing the waiter with your food might not have quite the same effect on your hunger levels.  But why is that?


It turns out that activity in the hunger neurons is rapidly silenced when animals receive food, which means that the negative affect is also suppressed1,2. Researchers at the National Institute of Diabetes and Digestive and Kidney Diseases investigated what would happen to these neurons if mice had access to high-fat, high-sugar food for 8 weeks, and then returned to eating normal food – the mouse version of returning home after a vacation in Italy3. Before mice had access to the high-fat food, the presentation of normal food to hungry mice caused a dramatic decrease in the activity of the hunger neurons, as expected. After exposure to the high-fat food, however, the normal food only slightly decreased activity of the hunger neurons (see Figure 1). When subsequently presented with some of the high-fat, high-sugar food, the activity was further reduced to pre-exposure levels. This pattern occurred as early as one week after exposure to the high-fat, high-sugar food and continued even after the mice were returned to their normal food for two weeks. These results suggest that exposure to this unhealthy food had rapid and long-lasting effects on normal food’s ability to quell hunger in mice. If high-fat, high-sugar food had an effect on the area of the brain that creates the negative feelings of hunger, does it also influence the part of the brain that makes food rewarding?


Craving sweets

Eating food, especially when we are hungry or eating something that tastes good, is extremely rewarding. This is in part due to the brain’s dopamine system. Dopamine is a chemical released from neurons in the midbrain during a positive experience, such as eating delicious food. Mice also get a surge of dopamine when they receive food, especially if they’re hungry. What happens, though, after exposure to the high-fat, high-sugar food? The researchers found that after 4 weeks on the high-fat food, a pellet of the normal food evoked less dopamine release than it had before the change in diet. The normal food was less rewarding after mice had experienced the more palatable diet for four weeks (see Figure 1). Interestingly, the dopamine released in response to a pellet of the high-fat food remained stable, and even increased slightly when the animals were returned to their normal food.

Figure 1. High-fat food alters response of hunger and dopamine neurons to food. Before exposure, food (A) decreases activity in hunger neurons and (B) increases activity in dopamine neurons. After exposure to high-fat food, these responses are dampened, simultaneously resulting in sustained hunger and decreased food reward.

This new study provides some insight into why dieting is so challenging. Exposure to foods high in fat and sugar works against you in two ways- by making healthier food less capable of suppressing the unpleasant feelings of hunger, and by making healthier food trigger less dopamine release and thus be less rewarding. One major question remains- how do foods high in fat and sugar alter these brain areas?  When nutrients are sensed in the gut, the cells in the intestines release hormones that signal to the brain that food has been consumed. It has been suggested that foods high in fat and sugar may blunt the response of these-hormone releasing cells in the gut, or make the neurons in the brain that sense them less responsive4,5. Further research linking the food itself with the effects on the hypothalamus and midbrain is needed. However, this work identifies two areas of the brain that together could be targeted to create more effective weight-loss strategies that do not enhance hunger or dampen the reward value of food.





  1. Betley, J.N., Xu, S., Cao, Z.F.H., et al. Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521, 180-185 (2015).
  2. Chen, Y., Lin, Y.C., Kuo, T.W., Knight, Z.A. Sensory detection of food rapidly modulates arcuate feeding circuits. Cell 160, 829-841 (2015).
  3. Mazzone, C.M., Liang-Guallpa, J., Li, C., et al. High-fat food biases hypothalamic and mesolimbic expression of consummatory drives. Nat Neurosci. 10.1038/s41593-020-0684-9 (2020).
  4. Daly, D.M., Park, S.J., Valinsky, W.C., Beyak, M.J. Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse. The Journal of Physiology 589, 2857-2870 (2011).
  5. Wall, K.D., Olivos, D.R., Rinaman, L. High Fat Diet Attenuates Cholecystokinin-Induced cFos Activation of Prolactin-Releasing Peptide-Expressing A2 Noradrenergic Neurons in the Caudal Nucleus of the Solitary Tract. Neuroscience doi: S0306-4522(19)30647-5 (2019).



Cover photo by Thought Catalog on Unsplash

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