Collaborators Focus on Interactions Among Diet, Obesity and Stress

We’re all familiar with terms such as "comfort food” and "stress eating,” but is there really a scientific basis for the link between obesity-related metabolic disease and stress-related psychological disorders? Two College of Medicine faculty members say the answer is clearly yes, based on current literature and their own collaborative investigations.

Yvonne Ulrich-Lai, PhD, an assistant professor in the UC Department of Psychiatry and Behavioral Neuroscience, and Karen Ryan, PhD, an assistant professor in the UC Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, collaborate at UC’s Reading Campus, focusing on interactions among diet, obesity and stress. Both receive research support from the National Institutes of Health.

In a recent perspective paper for the journal Cell Metabolism, they gave an overview of those interactions, including a review of current literature, discussion of the role of reward-driven food intake and consideration of important implications in the development of therapies for metabolism- or stress-related disease.

"I’m by training primarily a stress researcher and I have interest in how a person’s metabolic status affects the ability to cope with stress,” says Ulrich-Lai. "Karen is primarily more of a metabolism/obesity researcher, and she has interest in how that interacts with stress. So together, we have complementary expertise in both topics.”

Put more simply: They can offer sophisticated insight into why you might find yourself reaching for that fifth Girl Scout cookie when you hear the boss’s footsteps approaching.

For example, in a 2010 study published in PNAS, the official journal of the National Academy of Sciences, Ulrich-Lai and colleagues showed that pleasurable activity—including food—reduces stress by inhibiting anxiety responses in the brain. The research also indicated that the reduced-stress effects continued for at least seven days, suggesting a long-term benefit.

In the Cell Metabolism paper,  "Neuroendocrine Circuits Governing Energy Balance and Stress Regulation: Functional Overlap and Therapeutic Implications,” Ulrich-Lai and Ryan cited separate studies showing that obesity during the baseline period increased the risk of developing depression and that depression increased the odds for developing  obesity over time.

"Such associations likely arise … because neural circuits governing energy balance and stress reactivity are substantially intertwined, providing stress regulatory systems priority to redistribute fuels in response to acute threats (or perceived threats) to an individual’s well-being,” Ulrich-Lai and Ryan wrote.

The authors point out that these interrelationships have important therapeutic implications, "underscoring the importance of assessing the stress regulatory effects of metabolic therapies, as well as the metabolic consequences of potential therapies for stress-related disorders.”

As Ulrich-Lai puts it: "Available research suggests that as you develop a new therapy for one set of disorders, you should be considering potential effects on the other systems.”

Ryan notes that the endocannabinoid receptor (CB1) antagonist rimonabant, prescribed for the treatment of obesity, was withdrawn from the European market in 2009 and was not approved in the United States because its use was associated with significant increase in symptoms of depression, anxiety and suicidal thoughts.

"There’s some interest in asking whether or not you can avoid the brain side effects by targeting the appropriate receptors in peripheral tissues,” she says. "The question becomes, can that approach contribute to weight loss, and if you can create an effective compound that doesn’t get into the brain could that potentially have a better side-effect profile?

"But I think we would argue that the energy balance is so tightly regulated by the brain that even if you’re targeting a peripheral tissue, eventually you’re going to elicit changes in metabolic signals that may act in the brain.”