Depression wears many faces—some sad, some silent. But could it also wear a shape?
In two new studies exploring the hidden links between body composition and mental health, researchers are uncovering how where fat resides in the body—not just how much of it there is—may play a vital role in shaping our mood. Their findings are part of a growing effort to untangle the biology behind depression, especially in a world where obesity and mental illness often overlap but don’t always align in obvious ways.
The first study, published in Nature Metabolism, dives deep into molecular biology, connecting fat metabolism with stress responses in mice. The second, appearing in the Journal of Affective Disorders, offers a sweeping epidemiological view, analyzing detailed body scans and depression scores in over 10,000 Americans. Together, these studies form a compelling picture: fat may be more than an energy store. It may affect your emotions.
Fat That Talks Back
Logan Townsend and colleagues at McMaster University weren’t trying to study depression per se. They were following a biochemical trail left by stress.
In their study, they exposed mice to acute psychological stress and observed an intriguing response. The mice’s white fat tissue, especially the kind around the abdomen, began releasing, after lipolysis, a signaling molecule called GDF15. Within an hour, GDF15 surged in the blood—and the mice showed signs of heightened anxiety. When the scientists blocked the receptor for GDF15 in the brain stem, the anxiety response disappeared.
Adrenaline, the stress hormone, triggered fat cells to break down, releasing fatty acids. These, in turn, activated nearby immune cells—specifically, a type of macrophage known as M2-like—which secreted GDF15.
GDF15 is no stranger to stress. It’s known to suppress appetite and induce nausea in certain settings. But here, it did something else: it made mice anxious. The researchers concluded that this identifies a new axis—lipolysis to GDF15 to anxiety—that hadn’t been appreciated before.
Put simply, when the body is under stress, fat tissue becomes an active communicator—releasing chemical signals like GDF15 that travel through the bloodstream and activate specific areas in the brain involved in mood and anxiety.
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Regional Fat and Risk of Depression
While Steinberg’s study worked in mice and focused on acute stress, a separate research team led by Wenjun Gu in China (Journal of Affective Disorders) took a very different approach. They looked at chronic depression in humans.
Using full-body DXA (bone density) scans from the National Health and Nutrition Examination Survey (NHANES), Gu and his co-authors analyzed data from 10,694 American adults. They examined not only how much fat people carried but also its placement: legs, trunk, head, abdomen, hips.
The result? People with the highest percentage of total body fat were significantly more likely to report symptoms of depression. But the location mattered. Fat in the legs, gynoid region (hips and thighs), and even the head had the strongest links with depression. Surprisingly, this connection was especially pronounced in men and in individuals who were either underweight or overweight—but not those with a “normal” BMI.
The study used the Patient Health Questionnaire-9 (PHQ-9), a commonly used tool to assess depression symptoms. Even after adjusting for variables like income, physical activity, and chronic illness, the patterns held.
Fat’s Mood-altering Machinery
While the two studies were conducted independently, the overlap is striking.
In mice, fat tissue actively contributes to stress signaling by releasing GDF15, which then engages brain pathways tied to anxiety. In humans, certain regional fat deposits correlate more strongly with depression than others. Though causality cannot yet be claimed, both studies suggest that body fat—especially in certain places—may influence how we feel.
Why would fat affect mood?
One biological theory centers on inflammation. Fat tissue, especially when excessive or dysfunctional, releases inflammatory molecules that can cross into the brain and disrupt neurotransmitter systems. Another theory focuses on hormones like leptin and GDF15, which regulate hunger, metabolism, and stress.
But social factors must not be overlooked. Stigma, body image dissatisfaction, and reduced mobility can all affect mental health. That might explain why men—who generally have less visible fat in the hips and thighs—showed a stronger link between gynoid fat and depression in Gu’s study.
Where the Science Is Headed
Both teams acknowledge their limitations.
Gu’s study is cross-sectional, which means it captures a snapshot in time. It can’t tell whether fat causes depression or vice versa. Depression, after all, can alter eating patterns and physical activity levels, which in turn affect fat distribution.
The mouse study is more mechanistic but operates in a controlled, acute-stress setting. It’s unclear how these findings map onto the slow, insidious development of clinical depression in humans.
Still, the insights from both are valuable. They suggest that body composition—and particularly fat’s biological activity—deserves closer attention in mental health research.
Future studies could track fat changes over time and use brain imaging to see specifically how different fat regions affect neural circuits. Clinical trials might explore whether targeted fat reduction through diet or exercise has a measurable impact on mood. And the GDF15 pathway, now implicated in anxiety, could become a target for treating stress-related disorders.
