Scientists discover hidden link between body fat and anxiety

A new study has discovered a surprising molecular pathway that links the body’s fat cells to feelings of anxiety and may revolutionize our understanding of how physical and mental health intertwined. Researchers at McMaster University have identified specific hormones released from fat tissue during stressful times, direct exposure to anxiety-like behaviors.

The groundbreaking study, published April 15 in Natural Metabolism, reveals how psychological stress initiates a series of biological responses that begin in adipose tissue that ultimately affects brain function.

“Understanding the link between adipose tissue and anxiety opens new avenues for research and potential treatment,” said Gregory Steinberg, senior author and professor in McMaster’s Department of Medicine. “Our findings highlight the complex interactions between metabolism and mental health, which we hope will lead to better outcomes for those suffering from anxiety.”

The finding is at a critical moment, as anxiety disorders have increased rapidly over the past two decades and now affect nearly 30% of the Western population.

Through a series of experiments with mice, the researchers found that when the body undergoes stress, fat cells undergo a process called lipolysis, which is actually the breakdown of stored fat. This process releases fatty acids into the bloodstream, which then stimulates certain immune cells in the adipose tissue to secrete a hormone called growth differentiation factor 15 (GDF15).

This hormone is transmitted through the blood and communicates with the brain through a specific receptor called GFRAL, which is found only in the brain stem. When mice lacking this receptor were stress-tested, they showed significantly reduced anxiety behavior compared to normal mice, suggesting a critical role of GDF15 in anxiety responses.

“These findings are exciting possibilities for developing new anxiety therapies by focusing on metabolic pathways,” explains Logan Townsend, first author and postdoctoral researcher at McMaster. “By understanding how stress-induced adipocyte changes affect anxiety, we can explore innovative therapeutic strategies for these metabolic processes, providing more effective and targeted relief for individuals with anxiety disorders.”

This study specifically identified visceral fat (the internal fat around the internal fat), which is the main source of this incorrect connection of stress, rather than subcutaneous subcutaneous fat. This may help explain why some body fat distributions may differ in their mental health.

What makes this discovery particularly interesting is that it identifies previously unknown communication pathways between surrounding tissue and the brain during stressful times. The study found that the pathway works with stress response systems established by adrenaline and cortisol.

GDF15-activated brain regions include the central amygdala and the bed nucleus at the end of the plasmid, which is well known to be associated with anxiety responses. This suggests that while the initiation signal comes from adipose tissue, it ultimately affects the same neural circuits that regulate fear and anxiety.

The researchers used blood samples from obese children to confirm the correlation of their findings and compared children with or without a diagnosis of clinical anxiety. A complementary study was also conducted using genetic data from the UK biobank, which showed the association between GDF15 gene variants and anxiety traits.

Townsend added that the potential applications are beyond the scope of basic science: “Several companies are developing blockers for GDF15 to treat cancer, so these companies may also find anxiety.”

The study represents an interdisciplinary collaboration, with a significant contribution from Marc Jeschke of Hamilton Health Sciences and Pediatric Blood Samples led by McMaster’s Professor of Pediatrics.

This study opens a new chapter in understanding an anxiety disorder, which shows that metabolic and mental health are more deeply understood than before. For the millions of dollars suffering from anxiety around the world, these findings offer hope that targeted metabolic pathways can one day provide relief in the case of traditional psychiatric approaches.