21 . 07 . 2018

The Neurobiology of Appetite - Part I

Obesity and excess weight are increasingly frequent problems in today’s world. If the solution is as simple as creating a caloric deficit by eating less and/or exercising more, then why do many of us remain unable to achieve and maintain our ideal weight?

It seems that the answer isn’t that straightforward, as it is often the case with these health related questions.

It sounds logic that when the goal is to keep a healthy weight, no one wants to overeat. Why aren’t our beliefs and will power enough to prevent that from happening?

In reality, adiposity (body fat) control depends much more on instinctive and unconscious brain mechanisms than on our will power or any other rational and logic process. The human species evolved throughout most of its history in environments of limited resources, where food wasn’t abundant. In this setting, obtaining and storing calories was crucial, otherwise reproduction and survival would be at risk. These evolutionary pressures shaped our brain, specifically its most primitive and instinctive parts, into a sort of calorie searching “GPS” capable of directing our physiology and behavior in a tremendous way.


In reality, adiposity control depends much more on instinctive and unconscious brain mechanisms than on our will power or any other rational and logic process.”


The problem arose when the human being started to be surrounded by calorie dense foods, as it happens in the modern world. To the instinctive part of our brain, eating these foods seems like an obvious choice since it helps us guaranteeing calories, and therefore survival. Unfortunately, these unconscious mechanisms didn’t evolve to prevent fat accumulation, or at least not on the same scale.


 Highly processed foods are an innovation to the human species, from an evolutionary perspective.


Let’s describe the main, currently identified, adiposity control mechanisms our brain has at its disposal:

  • Reward system – located in the basal ganglia, this is the chief circuit responsible for addictive behavior. There is a release of dopamine in these neurons following the satisfaction of certain impulses, that our brain learns to look for and replicate. Receiving many sensory inputs, this system evaluates the available options and, instinctively, promotes the ingestion of foods with certain characteristics that confer them a greater reward. Fat, sugar and salt content make a food highly rewarding, and that’s why the food industry combines these flavors to make us overeat.
  • Economic choice system – lies in the orbitofrontal cortex and ventromedial thalamus. It integrates costs and benefits from all parts of the brain and determines if an impulse is to be carried or not. Even though it also receives conscious inputs, when it comes to food calories and convenience seem to be the deciding factors.
  • Lipostat – lies in the hypothalamus and works as an adiposity regulator through its influence on appetite, behavior and metabolic basal rate. It receives its main input from leptin, which is a hormone produced by the adipocytes (fat cells). When leptin decreases, the brain interprets that signal as a reduction of the energy reserves and reacts by promoting calorie ingestion and decreasing physical activity. Other factors like the food reward value, protein content, physical activity and sleep quality are also important in the lipostat regulation. This is the system that generally sabotages calorie restricted diets as it is activated to restore the pre-diet weight and fat percentage.



 The hypothalamus harbors the neurons that constitute the lipostat, in addition to many other homeostatic control systems.


  • Satiety system – regulates how much food we can eat at a given meal by inducing the sensation of satiety. It is located in the brainstem and takes in cues from the digestive tract, specifically the volume, fiber and protein content of the food. Less calorie density (less calories delivered in the same unit of volume), high fiber and/or protein content, make a food more satiating. Nevertheless, the reward system can overcome this signal and prevent or delay satiety when a highly rewarding food is being eaten (this is why there is always room for a delicious dessert).
  • Circadian rhythm and sleep – complex circuit spread through the hypothalamus, brainstem and other brain regions, that influences the reward, economic choice and lipostat systems. When our meal and sleep schedule are out of step with the day-night cycle and our internal biologic “clock”, the eating behavior is affected. In those circumstances, we tend to prefer calorie dense and highly rewarding foods, which are bad choices for weight loss.
  • Threat response system – it is coordinated by the amygdala and allows us to deal with threatening situations by activating the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis, which is responsible for the production of cortisol. In our society, this response is frequently triggered by the chronic stressors we are all subject to. For certain people, the ingestion of calorie dense and highly rewarding foods has a calming effect and helps dampening the stress response, working as an unconscious form of self-medication.

None of these brain circuits we explored is sealed and they all communicate with each other, in order to facilitate the physiological response and behavior that our instinctive brain has determined to be the most appropriate. These mechanisms are variable amongst individuals: some have a strong tendency to accumulate fat, while others are “blessed” with a lipostat that takes care of burning excess calories.

Now that we have identified the key players in body fat regulation, in the second part of this article, we will explore the conscious processes that one can implement to achieve and maintain weight loss.


Guyenet, SJ. The hungry brain : outsmarting the instincts that make us overeat. Flatiron Books, 2017.

Whiten, A. Forever Fat Loss: Escape the Low Calorie and Low Carb Diet Traps and Achieve Effortless and Permanent Fat Loss by Working with Your Biology Instead of Against It. Archangel Ink, 2014

Lutter, Michael, and Eric J. Nestler. Homeostatic and Hedonic Signals Interact in the Regulation of Food Intake. The Journal of Nutrition 139.3 (2009): 629–632.

Categorias: Exercise, Nutrition, Obesity