Scientists Find Hidden Connection Between Body Fat and Anxiety

A new study has uncovered a surprising molecular pathway that links the body’s fat cells to feelings of anxiety, potentially revolutionizing our understanding of how physical and mental health intertwine. Researchers from McMaster University have identified a specific hormone released from fat tissue during times of stress that directly triggers anxiety-like behavior.

The groundbreaking research, published April 15 in Nature Metabolism, reveals how psychological stress initiates a cascade of biological reactions starting in adipose tissue that ultimately affects brain function.

“Understanding the link between adipose tissue and anxiety opens up new avenues for research and potential treatments,” says Gregory Steinberg, senior author and professor in the Department of Medicine at McMaster. “Our findings highlight the complex interplay between metabolism and mental health, and we hope this will lead to better outcomes for individuals suffering from anxiety.”

The discovery comes at a critical time, as anxiety disorders have rapidly increased over the last two decades, now affecting nearly 30% of the Western population at some point in their lives, according to the study.

Through a series of experiments with mice, researchers identified that when the body experiences stress, fat cells undergo a process called lipolysis—essentially the breaking down of stored fat. This process releases fatty acids into the bloodstream, which then stimulate certain immune cells within the fat tissue to secrete a hormone called Growth Differentiation Factor 15 (GDF15).

This hormone travels through the bloodstream and communicates with the brain through a specific receptor called GFRAL, which is found exclusively in the brainstem. When mice lacking this receptor were subjected to stress tests, they showed significantly reduced anxiety-like behavior compared to normal mice, demonstrating GDF15’s crucial role in anxiety responses.

“These findings open up exciting possibilities for developing new treatments for anxiety by focusing on metabolic pathways,” explains Logan Townsend, first author and postdoctoral fellow at McMaster. “By understanding how stress-induced changes in fat cells can influence anxiety, we can explore innovative therapeutic strategies that target these metabolic processes, potentially offering more effective and targeted relief for individuals suffering from anxiety disorders.”

The research specifically pinpointed visceral fat—the internal fat around organs—as the primary source of this stress-anxiety connection, rather than subcutaneous fat just beneath the skin. This may help explain why certain patterns of body fat distribution might influence mental health differently.

What makes this discovery particularly intriguing is that it identifies a previously unknown communication pathway between peripheral tissues and the brain during times of stress. The study found that this pathway works alongside, but distinctly from, established stress response systems like adrenaline and cortisol.

The brain regions activated by GDF15 include the central amygdala and the bed nucleus of the stria terminalis—areas long known to be involved in anxiety responses. This suggests that while the initiating signal comes from fat tissue, it ultimately influences the same neural circuits that regulate fear and anxiety.

Researchers confirmed the relevance of their findings using blood samples from children with obesity, comparing those with and without clinical anxiety diagnoses. There was also complementary research using genetic data from the UK Biobank that showed associations between GDF15 gene variants and anxiety traits.

Townsend adds that the potential applications extend beyond basic science: “Several companies are developing blockers of GDF15 for treating cancer, so it is possible these will find use for anxiety as well.”

The study represents a multidisciplinary collaboration, with significant contributions from Marc Jeschke of Hamilton Health Sciences and pediatric blood samples from research led by Katherine Morrison, professor in McMaster’s Department of Pediatrics.

This research opens a new chapter in understanding anxiety disorders, suggesting that metabolic health and mental health are more deeply interconnected than previously recognized. For the millions suffering from anxiety worldwide, these findings offer hope that targeting metabolic pathways could someday provide relief where traditional psychiatric approaches have fallen short.