Low Testosterone Combined with High-Fructose Diet May Accelerate Fatty Liver Disease, Study Finds - Video

Low testosterone levels combined with high fructose consumption may significantly increase fat accumulation in the liver, according to a new study. Researchers have discovered that changes in gut bacteria could play an important role in worsening fatty liver disease when hormonal imbalance and excessive dietary fructose occur together.

Published in the American Journal of Physiology-Endocrinology and Metabolism, the study investigated how reduced testosterone levels and fructose-rich diets interact to influence liver health.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition characterised by excessive fat accumulation in the liver. Risk factors include obesity, type 2 diabetes, hormonal disturbances and unhealthy dietary habits.

To investigate these effects, researchers conducted experiments involving eight-week-old male mice divided into six groups. Some mice underwent procedures to reduce testosterone levels, while others maintained normal hormone levels.

The animals received different dietary interventions, including fructose supplementation, with selected groups also receiving antibiotics to examine the role of gut bacteria.

The findings revealed that low testosterone levels and fructose consumption individually caused relatively modest changes in liver fat.

However, when combined, they significantly increased liver triglyceride accumulation and liver weight, indicating a stronger effect on fatty liver development.

Interestingly, antibiotic treatment reduced the increase in liver weight, suggesting that gut bacteria contributed to these metabolic changes.

Researchers also identified alterations in gut bacterial composition, changes in liver gene activity and increased levels of pyruvate, a compound involved in energy metabolism, within the intestine.

Further laboratory experiments using mouse liver cells revealed that pyruvate and fructose acted together to promote greater fat accumulation.

These findings suggest that altered gut bacteria may increase intestinal pyruvate production, potentially worsening liver fat accumulation in the presence of high fructose intake and reduced testosterone.

However, the experiments were conducted in mice and isolated liver cells, and further human studies are needed.

REFERENCE: Hiroki Takahashi, et al.; Testosterone deficiency synergistically exacerbates fructose-induced hepatic steatosis through gut microbiota and pyruvate in mice. American Journal of Physiology-Endocrinology and Metabolism, 2026; 330 (2): E233 DOI: 10.1152/ajpendo.00518.2025