How Overeating Changes the Brain

Are you wondering if this afternoon’s cheesecake is going to change your body? While most of us imagine it changing our waistline, few wonder whether it also changes the brain. But it does, and a recently published study (Rossi, 2019) shows us how.

The idea that the brain influences nearly everything we do should not be surprising; whom we like, how we feel, and even what we eat is affected by brain activity. Lying deep at the base of our brain lives a group of cells that comprise the hypothalamus. The hypothalamus orchestrates control over several behaviors related to the survival of the species; behaviors that, as I often tell my students, comprise the four F’s of hypothalamic regulation — fighting, fleeing, feeding, and mating.

Like most brain regions, the hypothalamus is divided into smaller structures; these are frequently named using words that point to directionality. Consider, for example, the lateral hypothalamus. Its name implies that it resides in the lateral portion of the hypothalamus, or away from the middle. Those of us interested in motivated behaviors know that to study the brain’s influence over feeding you will inevitably cross paths with the lateral hypothalamus. This is because the structure is crucial to facilitating or increasing eating. It does this by modulating metabolism, digestion, insulin secretion, and taste sensation, to name a few factors. The lateral hypothalamus is also highly conserved across species and thus suitable for modeling various aspects of human eating behavior. So when you think increased eating, think increased activity in your lateral hypothalamus.

This relationship was first evidenced in early non-human animal studies, which showed that rodents with damage to their lateral hypothalamus often refused to eat and, conversely, as one might expect, stimulating or activating this region elicited insatiable eating. The idiosyncrasies of the link between eating and the lateral hypothalamus have since been extensively studied and these details are beyond the scope of our discussion. Rest assured, however, that many excellent behavioral neuroscientists have dedicated an immeasurable number of hours to informing our understanding of how the lateral hypothalamus mediates eating and food reward. The article by Rossi and colleagues does just that, by showing how overeating remodels the lateral hypothalamus and how these changes then impact how we eat.

By combining a variety of cellular techniques, the experimenters examined whether a high-fat diet altered gene expression of cells in the lateral hypothalamus. The experiment was designed to compare gene expression of cells in mice receiving a high-fat diet versus those receiving a normal diet. They discovered altered gene expression as a result of obesity in a variety of cells within the lateral hypothalamus. However, the strongest obesity-induced genetic changes occurred in cells containing a protein called vesicular glutamate transporter type-2. Generally, these cells use a fast-acting excitatory brain chemical called glutamate. They examined these cells further and discovered that they are responsive to sugar consumption; however, the magnitude of response depended on the animals’ motivational state: How much food the animal wanted impacted how responsive the cells were to sugar.

Pre-feeding the mice (low-motivational state) or introducing a 24-hour fasting condition (high-motivational state) before the experiment controlled motivation for food. The excitatory cells in the lateral hypothalamus of animals in the low motivational state (not hungry) experienced greater activation after sugar consumption than in animals that were fasting. This shows that food satiety influences the reward encoding for food occurring within the lateral hypothalamus.

What was most interesting about the coding profile of these excitatory cells was that a high-fat diet also altered their response rate. Namely, cells of animals on a regular diet maintained their ability to detect sugar consumption, but cells in mice on a high-fat diet became progressively less responsive to sugar; thus, the change in the brain.

These findings are novel and exciting, as they show that a high-fat diet alters encoding for a food reward in individual cells in the lateral hypothalamus. Moreover, we now see that a chronic high-fat diet modifies the lateral hypothalamus by deterring their neural response and thus weakening an endogenous “brake” on eating. In other words, a high-fat diet may change your brain to promote overeating.