High-fat Diet and Genetics Lead to Anxiety and Depression in Rats

Researchers suggest outbred rat model for studying genetics of obesity and anxiety

Rockville, Md. (August 4, 2020)—New research in a genetically diverse rat strain finds high-fat diet and genetics together increase anxiety and depression-like behavior in addition to negatively affecting metabolic health. The study is published ahead of print in Physiological Genomics.

Approximately 40% of adults in the U.S. are overweight or obese, making obesity a public health issue. Previous studies have shown strong links between obesity, diet and anxiety or depression, but the underlying reasons for these co-occurring conditions are unclear. Shared genetics may be one factor at play: Some of the chromosomal locations identified in the human genome associated with depression overlap with those associated with obesity and body mass index. Finding an animal model with genetic variability similar to that found in people is ideal to learn more about how these features intersect and influence one another.

Researchers measured the effects of high-fat diet on the metabolic health and emotional behavior in a type of rodent called the heterogenous stock rat. Because this animal strain is not inbred, it has a wide genetic diversity that more closely mimics the range of traits and characteristics found in humans relative to inbred models. One group of rats was fed a high-fat diet, while a control group consumed a low-fat diet. The research team measured the animals’ body weight, fat accumulation around the body (fat pad) and blood sugar levels. After 11 weeks, the researchers assessed coping response to stress or “despair-like behavior” using a swim test where immobility is typically associated with despair-like behavior.

The research team conducted a second study, with a separate group of high-fat–fed rats and low-fat controls, to look at additional behavioral tests. The tests were used to determine factors causing the increased immobility. An increase in fat pad size may cause physical limitations resulting in immobility, but the chronic high-fat diet could also contribute to despair-like behavior. In this study, both groups participated in weekly tests starting at week eight—a maze and an open field test used to measure anxiety, a test that prompts grooming habits and the previously described swim test used to measure despair-like behavior.

Unsurprisingly the high-fat–fed rats had more weight gain and fat accumulation, higher blood sugar levels and reduced glucose tolerance than the low-fat groups. Compared with the controls, the high-fat diet groups showed longer duration of immobility in the swim test, increased anxiety in the maze test and “anxious hyperactivity” in the open field test. These results suggest that diet, as well as increased fat pad size, plays a role in these emotional behaviors. Contrary to hypothesis, the high-fat–fed group did not show disinterest in grooming. In fact, they spent more time grooming than the low-fat–fed group. Whether this behavior was anxiety-induced is unclear.

These results “lay the groundwork for future investigation to identify genes and variants that predispose individuals to increased [obesity] and worsened metabolic and behavioral health specifically under high-fat diet conditions,” the research team wrote. “Given the high levels of obesity, the preponderance of high-fat diets worldwide and the complex interplay between obesity and behavioral health, having a model to study the underlying genetics of these traits is of extreme importance.”

Read the full article, “High fat diet negatively impacts both metabolic and behavioral health in an outbred rat model,” published ahead of print in Physiological Genomics.

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