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Do Fatty Foods Deplete Serotonin Levels?

A new study examines the molecular connection between diet and depression.

Nappy / Pexels
Source: Nappy / Pexels

Most of us are probably aware of the benefits of following diets rich in fruits, vegetables, and whole foods. But how concerned should we be about the fat content in our diet, especially as it pertains to mental health?

New research published in the journal Translational Psychiatry suggests that there is a robust relationship between high-fat diets and depression. Furthermore, this research attempts to pinpoint the precise way in which a diet high in fat can disrupt normal cognitive functioning.

To explore the association between high-fat diets and mental health, researchers at the University of California San Francisco, the University of Glasgow, and King's College exposed mice to a high-fat diet for a period of three to eight weeks. During this time, they tracked depression-like behavior, as measured by tail suspension tests and swim tests (two commonly used procedures to assess mood changes in mice in response to some type of experimental treatment). They compared results from the mice receiving a high-fat diet (60 percent of calories derived from fat) to a control group of mice that were fed normal diets.

As predicted, they found an increase in depression-like behavior in mice exposed to the high-fat diets at both the three- and eight-week time increments. Mice receiving the high-fat diet showed greater immobility in the tail suspension and swim tests. Immobility is indicative of one type of behavioral change typically associated with depression. Importantly, the immobility did not appear to be based on weight gain alone. Even though mice who were fed high-fat diets gained more weight than the control mice, weight, in general, was uncorrelated with the amount of immobilization during the tail suspension and swim tests. In other words, it was something about the alteration of brain chemistry, not physique, that made the mice exhibit depression-like behavior.

To understand what this alteration might be, the researchers examined various molecular pathways that could link high-fat diets to disrupted cognitive functioning. Using a series of screening techniques, the researchers found that mice exposed to the high-fat diet showed an accumulation of fatty acids in the hypothalamus. This, in turn, suppressed normal protein signaling.

The researchers write, "We found that the consumption of a fat-dense diet leads to an influx of dietary fatty acids specifically in the hypothalamus. These fatty acids can directly modulate the protein kinase A (PKA) signaling pathway that is responsible for the development of depression."

This finding is important for a number of reasons. For one, it identifies the molecular process through which high-fat diets can alter mood and behavior. According to the research, it's not that fatty foods negatively impact serotonin production (or the production of other neurotransmitters) directly. Rather, it appears that high-fat diets disrupt the normal functioning of the hypothalamus which, in turn, promotes symptoms associated with depression.

Furthermore, this research hints at new avenues for treating depression, especially in people who struggle with their weight. Developing molecules that restore normal functioning in the hypothalamus may, the authors write, "represent a new generation of antidepressants with increased specificity for either overweight and/or obese individuals."


Vagena, E., Ryu, J. K., Baeza-Raja, B., Walsh, N. M., Syme, C., Day, J. P., ... & Baillie, G. S. (2019). A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling. Translational psychiatry, 9(1), 141.

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