Metabolism and emotions: connecting the dots

Primitive human behaviors were the first evidence that led us to the conclusion that our metabolic state can directly affect our emotions. Hungry humans – and basically any other hungry animal – are encouraged to look for food. By suppressing the fear circuit, hunger gives even the most cautious living being the necessary “motivation” to explore even the most unknown spaces. Hunger seems to give us confidence. On the other hand, satiated humans are quite reluctant to take unnecessary risks since food is not an immediate necessity. Satiety increases the fear of the unknown and makes us anxious.

Some studies have already tried to explain how this link between metabolism and emotions works. The results? Rodents fed a diet rich in fat were more afraid of stimuli than the ones consuming a regular diet. The parallel to humans is similar. Patients with obesity have higher chances of developing anxiety disorder, but the ones submitted to a procedure that led to weight loss displayed reduced anxiety scores. Interesting, right? What does our metabolic status have to do with our feelings?

Metabolism involves all the chemical processes that go on in our organism.
Emotions are psychological states, which result from neurophysiological changes.

Today, we will scratch only the tip of an iceberg. This post will only focus on one aspect of our metabolism, fat metabolism, and on two aspects of our emotions, anxiety and depressive-like behavior. They are connected by many factors, but we will give special attention to two of them: the neuropeptide Y (NPT) and the glucagon-like peptide 1 (GLP-1).

Our body has a multitude of metabolic factors that play a role in maintaining our energy storage. These factors are mainly produced and secreted in organs such as the liver, fat tissue, pancreas, and gut. It seems natural to think that they will act only on these organs. However, some of them also play an essential role in our brain, thereby inducing changes to our emotions. The inverse situation is also true. Some molecules that are primarily inherent to the brain play a crucial role in regulating our energy storage pathways. The neuropeptide Y (NPY) and the glucagon-like peptide 1 (GLP-1) illustrate these dynamics. It feels like it will get complicated just by the name, but let’s navigate it together. 

The NPY is a neurotransmitter (a messenger that transmits signals from a neuron to somewhere else in the body). NPY has been identified as the most abundant peptide present in the mammalian central nervous system, which consists of the brain and the spinal cord. You may have heard about neuropeptides before. They have become quite famous since the discovery of their potential to treat anxiety, stress and other behavior-related issues. NPY has been shown to have an inverse relationship to anxiety: the more NYP you have, the less anxiety you feel. This is the basis for what we call NPY anxiolytic or calming effect.

However, the NPY also has other roles outside the brain environment. Studies have placed this neurotransmitter as an important player in food intake, obesity, cardiovascular regulation, and even immunity. We do not need to go through all of these branches, but let’s have a quick, curiosity driven look: evidence shows that NPY is associated with obesity through 1) stimulating food intake, 2) decreasing energy expenditure, and 3) increasing our fat storage. Updating the flow: the more NPY you have, the less anxiety you have, but… the more fat you have. One cannot have everything, but it is interesting to see how our bodies are always seeking balance: researchers also found out that physical exercise increases our ability to release NPY. This way the body gets what is good from both worlds: by exercising, you avoid body fat accumulation while decreasing anxiety via NPY secretion.

NYP is produced in the brain, acting mainly in the brain but connecting dots with our metabolism. What about a molecule not produced in the brain but capable of influencing it?

GLP-1 is a hormone produced and secreted in the gut. It exerts effects in many metabolic processes: production and secretion of insulin (check it out my previous post about insulin), gastrointestinal motility, generation of pancreatic islets cells (I have talked a bit about this topic before), energy balance, food intake (it suppresses our appetite!) and much more. GLP-1 also has a clinical use. It is now a treatment for type 2 diabetes and obesity.

But guess what? It has been shown that GLP-1 is also present in the brain. It is produced in neurons present in the hindbrain and (is suggested to be) produced by microglia (check our post about the microglia!). GLP-1 receptors (which is where the GLP-1 molecule must “connect” to trigger its biological functions) in the brain were found in areas responsible for the regulation of mood and emotionality. Still, how it acts in there is not yet settled. Studies performed in rodents that GLP-1 can influence learning and memory. Others – also performed in rodents – showed that while acute effects include an increase in anxiety, chronic treatment actually reduces depression-like behavior.

In summary, what do we now know? We know that NPY regulates anxiety, fat storage, and metabolism, and GLP-1 regulates energy balance and food intake, and possibly reduces depressive-like behavior. So what’s the point? Why are we talking about this? There is a high prevalence of depression, anxiety and other mood disorders in patients with obesity. Moreover, it has been already demonstrated that anti-obesity treatments have a negative effect on mood. These are the most important associations to support more investigations in the field of neuroendocrinology (the branch of physiology that studies the interaction between the nervous system and the endocrine system – our metabolism!). Molecules such as NPY and GLP-1 may have an even more significant direct relevance to the clinic, which may be especially useful to patients suffering with both obesity and depression.

Do not forget: science is changeable, transforming and in constant construction.
Do you feel like learning more about any specific molecule? Do you have a question, curiosity, suggestion or remark? Leave a comment!
See you in our next blog post!