Obesity associated with anxiety and cognitive impairment in mice

With rates of obesity and anxiety both on the rise-especially among younger Americans-new research suggests that the two conditions may be connected through interactions between the gut and the brain. The study, conducted in mice, links diet-induced obesity with anxiety-like symptoms, alterations in brain signaling and differences in gut microbes that may contribute to impaired brain functioning.

Several studies have pointed to a link between obesity and anxiety, though it is still unclear whether obesity directly causes anxiety or if the association is influenced by societal pressures. Our findings suggest that obesity can lead to anxiety-like behavior, possibly due to changes in both brain function and gut health."

Desiree Wanders, PhD, associate professor and chair of nutrition at Georgia State University

Wanders will present the findings at NUTRITION 2025, the flagship annual meeting of the American Society for Nutrition held May 31–June 3 in Orlando, Florida.

While it is well established that obesity can lead to conditions like type 2 diabetes and heart disease, the potential impacts on brain health are less clear. To probe the connections between obesity, cognitive function and anxiety, the researchers designed a series of experiments using a mouse model that develops many of the same obesity-related issues seen in humans.

The study included 32 male mice. From 6 to 21 weeks of age-a period equivalent to adolescence into early adulthood in humans-half of the mice were fed a low-fat diet and half were fed a high-fat diet. By the end of this period, mice on a high-fat diet weighed significantly more and had significantly more body fat than those fed a low-fat diet.

In behavioral tests, the researchers found that the obese mice displayed more anxiety-like behaviors, such as freezing (a defensive behavior mice exhibit in response to a perceived threat), compared with lean mice. These mice also showed different signaling patterns in the hypothalamus, a region of the brain involved in regulating metabolism, which could contribute to cognitive impairments.

In addition, the researchers observed distinct differences in the makeup of gut bacteria in obese mice compared with lean mice. These findings align with a growing body of evidence pointing to the role of the gut microbiome in regulating behavior.

While recognizing that research in mice does not always translate directly to humans, Wanders said that the results provide new insights that underscore the importance of targeting multiple systems in understanding and potentially treating obesity-related cognitive impairments.

"These findings could have important implications for both public health and personal decisions," said Wanders. "The study highlights the potential impact of obesity on mental health, particularly in terms of anxiety. By understanding the connections between diet, brain health and gut microbiota, this research may help guide public health initiatives that focus on obesity prevention and early intervention, particularly in children and adolescents." 

Wanders also noted that the carefully controlled conditions used in the study lend rigor and credibility to the results but added that the real world is much more complex.

"While our findings suggest that diet plays a significant role in both physical and mental health, it is important to remember that diet is just one piece of the puzzle," said Wanders. "Environmental factors, genetics, lifestyle choices and socioeconomic status also contribute to the risk of obesity and its associated health outcomes. Therefore, while these results are important, they should be considered in the context of a broader, multifactorial approach to understanding and addressing obesity-related cognitive impairments and mental health issues."

Next, the researchers hope to further explore the mechanisms by which diet-induced obesity affects the brain and behavior by digging deeper into the changes in the gut microbiome and expanding their study to include female mice and different age groups. Wanders added that it would be useful to determine whether weight loss interventions could reverse the impacts.

Wanders will present this research at 11:45 a.m. - 12:45 p.m. EDT on Sunday, June 1, during the Obesity session at the Orange County Convention Center.