Potbelly May Be a Sign of More Than Just Weight Gain

People who carry excess fat around the stomach are prone to obesity-related health issues. Now, a study suggests that having a so-called pot belly may also be a sign of brain aging.

Newsweek spoke to one of the lead researchers, Yoshinori Takei, about the study, which revealed that a specific type of belly fat (called visceral fat) plays a surprising role in brain health.

This fat releases a protein called CX3CL1, which in turn helps produce brain-derived neurotrophic factor (BDNF)—a protein that helps nerve cells survive and grow.

We also spoke to gastroenterologist Dr. Shawn Kodadadian, who explained that a potbelly develops when excess fat accumulates in the abdominal area, causing the stomach to protrude. He shared the key reasons behind this and how it can be reduced.

How Do People Develop a Potbelly?

Kodadadian told Newsweek that a potbelly is due to a combination of factors, such as:

• Excessive calorie intake (high amounts of processed foods, sugary drinks, alcohol, and unhealthy fats)
• Insufficient exercise
• Hormonal changes

The medical director at Manhattan Gastroenterology in New York explained: “Normal aging can also slow metabolism, making it easier to gain weight.

“High cortisol from chronic stress can promote fat storage, as well as low testosterone in men and menopause-related estrogen changes in women.

“Gas, constipation, and fluid retention can also make the belly appear larger and contribute to the pot belly appearance.”

The Study

Takei and colleagues found that, in young mice, this fat-to-brain connection works smoothly, helping to maintain good cognitive health. But as mice get older, their fat tissue makes less proteins that help the body’s immune system fight infection and inflammation (CX3CL1), which leads to lower levels of BDNF, a protein in the brain that helps nerve cells survive and grow.

Since BDNF is linked to memory and thinking skills in older adults, this drop may contribute to cognitive decline with age. Encouragingly, restoring CX3CL1 levels has been shown to improve brain function in aging mice.

Takei said: “BDNF is a small protein that promotes the viability and functional integrity of neurons in the hippocampus.

“As the hippocampus is the part of the brain responsible for memory formation and mental health, its deficiency can be observed in patients with Alzheimer’s disease and in patients with major depressive disorder. Moreover, it has been reported that higher brain BDNF expression is associated with slower cognitive decline in older adults.”

How Is Excess Abdominal Fat Linked to Brain Aging?

Visceral adipose tissue plays a role in maintaining brain-derived neurotrophic factor (BDNF) levels, which are essential for brain function and neuronal survival. However, the ability of visceral fat to influence BDNF expression declines with age. This suggests that while visceral fat may have a protective effect on brain health, this effect weakens over time, potentially contributing to age-related cognitive decline.

Kodadadian told Newsweek: “Excess abdominal fat, especially visceral fat (fat stored deep in the abdomen around organs), is strongly linked to brain aging through multiple biological mechanisms.

“Visceral fat release pro-inflammatory chemicals (cytokines, etc.) which can damage brain cells. Further, studies have shown that people with more abdominal fat have smaller brain volumes especial in areas related to memory and decision making.”

Middle-Aged People and Cognitive Decline

Takei explained that as people reach middle age, their bodies become less responsive to certain hormones that help break down fat (called catabolic hormones).

These hormones—such as adrenaline, cortisol, and glucagon—normally trigger fat burning in white fat tissue. However, because middle-aged adults are less sensitive to these hormones, it becomes harder for them to lose weight.

The study suggests that one reason for this could be the reduced activity of an enzyme called 11β-HSD1 in visceral fat (VAT). This enzyme helps regulate how fat tissue responds to glucocorticoids (a type of catabolic hormone). When VAT becomes less sensitive to glucocorticoids, it also produces lower levels of a protein called CX3CL1. This reduction in CX3CL1 may then lead to lower levels of BDNF, a protein essential for brain health.

In simpler terms, people who struggle to lose weight between the ages of 40 and 60 may also have lower levels of CX3CL1 and BDNF, which could contribute to faster cognitive decline as they get older.

How To Reduce a Pot Belly?

To reduce a pot belly, one should improve one’s diet by cutting back on sugar and refined carbohydrates like white bread and rice. Kodadadian suggests increasing protein intake and drinking plenty of water to reduce bloating and boost metabolism.

Regular exercise is also key. Strength training, in particular, helps build muscle and enhance metabolism. Engaging in 30–45 minutes of exercise daily can support fat loss.

Kodadadian told Newsweek: “Reducing stress and improving sleep habits can also be helpful via their effects on hormone balance in the body.”

Takei agrees and emphasizes the importance of maintaining healthy belly fat. He explained the science behind it.

He said: “We found that an enzyme called 11β-HSD1, which is present in belly fat, plays a key role in maintaining brain health by supporting a protein called BDNF in the hippocampus (a part of the brain important for memory and learning).

“However, when a person becomes obese, the levels of 11β-HSD1 in belly fat increase too much. This is a problem because excessive 11β-HSD1 is linked to belly fat accumulation and metabolic issues like diabetes.

“Overall, our study shows that maintaining healthy belly fat is important for keeping the brain in good shape as we age.”

While these findings provide researchers with a better understanding of brain and metabolic health, there is one obvious limitation: the study was conducted on mice.

He said: “Evidence from humans is essential for clinical application.”

Reference

Takei, Y., Amagase, Y., Goto, A., Kambayashi, R., Izumi-Nakaseko, H., Hirasawa, A., & Sugiyama, A. (2025). Adipose chemokine ligand CX3CL1 contributes to maintaining the hippocampal BDNF level, and the effect is attenuated in advanced age. GeroScience. https://doi.org/10.1007/s11357-025-01546-4