How Testosterone Levels May Influence Sugar’s Effects on the Liver

New research indicates that lower testosterone could leave the liver more vulnerable to sugar. In mice, scientists found that reduced testosterone together with a high-fructose diet made fatty liver disease worse, with gut bacteria possibly playing a role.

According to a study from Osaka Metropolitan University, hormones, diet and gut health may interact in ways that affect the liver. However, the findings have not yet been verified in humans.

Lower Testosterone and Fructose Linked to Worse Fatty Liver

When too much fat accumulates in the liver, it is known as fatty liver. It is an early sign of metabolic dysfunction-associated steatotic liver disease, or MASLD, a condition tied to obesity, type 2 diabetes and low testosterone.

The researchers looked at how testosterone and fructose affected the livers of 8-week-old male mice. Some mice were castrated to reduce testosterone, while others underwent a sham procedure. The animals were then separated into groups based on diet and whether they received antibiotics.

The study showed that mice with lower testosterone developed greater liver fat buildup when they ate fructose. The combined impact was stronger than either factor alone, suggesting that low testosterone may intensify the liver’s reaction to a high-fructose diet.

The team also detected shifts in the gut microbiome of mice exposed to both low testosterone and fructose. Those changes were associated with higher levels of pyruvate in the gut, a substance involved in energy metabolism.

In related experiments, scientists examined how pyruvate and fructose affected mouse liver cells. They found that the two substances acted together to promote the buildup of neutral fats inside the cells. Antibiotics also appeared to blunt some of the effects seen in mice, adding support to the idea that gut bacteria are involved.

Possible Implications for Men’s Liver Health

The findings may help researchers better understand how hormonal shifts and dietary patterns can combine to influence liver health. In particular, the role of gut pyruvate could open a new path for studying potential therapies and dietary approaches.

Researchers now hope to learn more about how pyruvate encourages fat buildup in liver cells. Over time, that knowledge could help lead to new ways to prevent or treat fatty liver disease.

Still, the work was done in mice and in isolated mouse liver cells. Further studies are needed to determine whether the same mechanism exists in humans, and whether targeting gut bacteria or pyruvate could help protect the liver.