People with obesity are often likely to develop depression as well, but the mechanisms at play are still unclear. New research in mice may now explain what happens in the brains of individuals who have a high-fat diet.
So far, though, it has remained unclear exactly why this is the case, and what biological mechanisms might drive obesity-related depression.
A team of researchers from the University of Glasgow in the United Kingdom and the Gladstone Institutes, in San Francisco, CA, has recently studied how eating a diet high in saturated fats might make depression more likely, using mouse models to do so.
The investigators — led by Prof. George Baillie, from the University of Glasgow — note that this is a particularly important research topic, as obesity-related depression seems to happen via different mechanisms from depression in otherwise healthy individuals.
In its study paper, which appears in the journal Translational Psychiatry, the research team explains that many people with obesity and depression, who doctors treat with regular antidepressants, do not see any benefits from the treatment.
At the same time, people with obesity and depression also do not experience some of the side effects that people typically associate with those antidepressants, such as further weight gain.
“When compared with patients of normal body weight, overweight and obese patients showed a substantially slower response to antidepressant treatment, less improvement in neuroendocrinology and cognitive processing, and less antidepressant-induced weight gain,” the researchers write.
So, what happens in the brains of people who are overweight or have obesity that makes them more susceptible to depression?
To gain a basic idea, the research team conducted a preliminary study in mouse models to which the scientists fed a high-fat diet, containing up to 60% of both saturated and unsaturated fats.
The brains of mammals, including humans, actually need certain fatty acids —such as omega-3 — to function correctly. Humans bodies, in particular, cannot synthesize fatty acids on their own, and so they need to absorb these nutrients from food.
However, not all fatty acids are as healthful, and the overaccumulation of fatty acids in the body can lead to health problems.
In the current study, the researchers looked at how fatty acids accumulated in the brains of the mice eating the high-fat diet, and whether these substances affected mechanisms that scientists tie to mental health and changes in behavior consistent with the presence of depression.
Soon enough, the team found that the mice in their studies experienced an influx of palmitic acid to a region of the brain known as the hypothalamus, which regulates the release of various hormones into the bloodstream.
Palmitic acid is a common saturated fatty acid that is present in many different foods and ingredients, including palm and olive oil, cheese, butter, margarine, and some meat products.
According to previous research, this fatty acid may explain the link between obesity and an increased risk of cardiovascular problems.
Through the current study, the investigators have uncovered another role — it seems the high levels of palmitic acid in the hypothalamus alter a signaling pathway that researchers associate with traits of depression. This pathway, known as cAMP/PKA, is involved in many metabolic processes, including dopamine signaling, which, in turn, contributes to the regulation of emotions.
Thus, in mice at least, the researchers were able to confirm that the absorption of certain dietary fats has a direct impact on brain-signaling pathways that influence the development of depression.
“This is the first time anyone has observed the direct effects a high-fat diet can have on the signaling areas of the brain related to depression,” says Prof. Baillie. “This research may begin to explain how and why obesity is linked with depression, and how we can potentially better treat patients with these conditions,” he adds.
The team believes that the mechanism it observed in mice is probably also at play in humans with obesity-related depression. The connection between a poor diet and poor mental health makes sense, according to the lead author.
“We often use fatty food to comfort ourselves as it tastes really good, however, in the long term, this is likely to affect one’s mood in a negative way. Of course, if you are feeling low, then to make yourself feel better you might treat yourself to more fatty foods, which then would consolidate negative feelings.”
Prof. George Baillie
The current findings also gave the researchers a clue as to how to potentially treat obesity-related depression more effectively.
Elsewhere in the study, they decided to try reducing levels of an enzyme known as phosphodiesterase, which usually breaks down cAMP — short for cyclic AMP, an intercellular “messenger.”
This approach allowed them to protect the mice from developing behaviors consistent with the presence of depression.
In the future, the researchers hope that these findings will help experts to develop better treatments or preventive approaches against obesity-related depression.
“We all know that a reduction in fatty food intake can lead to many health benefits, but our research suggests that it also promotes a happier disposition,” says Prof. Baillie.
“Further to that, understanding the types of fats, such as palmitic acid, which are likely to enter the brain and affect key regions and signaling will give people more information about how their diet can potentially affect their mental health,” he emphasizes.