Low testosterone could make sugary diets more harmful for liver: Study

A new study suggests that low testosterone and high fructose intake may combine to accelerate fatty liver disease by altering gut microbiota and boosting pyruvate levels

Low testosterone combined with a high-fructose diet may significantly increase fat build-up in the liver, potentially worsening metabolic dysfunction-associated steatotic liver disease (MASLD), according to new research conducted on mice.

 

The study, titled Testosterone deficiency synergistically exacerbates fructose-induced hepatic steatosis through gut microbiota and pyruvate in mice, published in the journal Scientific Reports, suggests that when testosterone levels drop, the body may become more vulnerable to the harmful metabolic effects of fructose, a sugar commonly found in sweetened drinks and processed foods. Researchers at Osaka Metropolitan University, Sakai, Osaka, Japan, observed that the two factors together worsened fatty liver changes, highlighting a complex interaction between hormones, diet, gut bacteria, and metabolism.

 

What is fatty liver disease and why is it becoming more common?

Fatty liver disease, now called metabolic dysfunction-associated steatotic liver disease (MASLD), occurs when excess fat accumulates in liver cells. It is considered the earliest stage of liver damage linked to metabolic disorders.

 

According to the researchers, globally MASLD is rising rapidly. The condition is strongly associated with:

• Obesity
• Type 2 diabetes
• High fructose consumption
• Hormonal changes such as low testosterone

While these risk factors are well known individually, researchers have long suspected that their combined effects may be far more harmful than each factor alone.

What did the study find about testosterone, fructose and liver fat?

The researchers highlighted that low testosterone has been linked to metabolic disorders, including obesity, insulin resistance, and fatty liver disease in previous studies. At the same time, diets high in fructose, commonly found in sugary beverages, packaged snacks, and processed foods, are known to promote fat accumulation in the liver.

 

However, researchers still lacked clear evidence about how these two factors interact inside the body.

 

To explore this, scientists used eight-week-old male mice and created two hormonal conditions:

• Normal testosterone levels (sham-operated mice)
• Testosterone deficiency (castrated mice)

They found that individually, low testosterone or high fructose intake caused only minor changes in liver triglyceride levels. But when both occurred together, their effects combined and amplified each other.

 

Mice that had both testosterone deficiency and high fructose intake developed significantly heavier livers with greater fat accumulation, a hallmark of fatty liver disease.

 

They also found that when antibiotics were given, the increase in liver weight was reduced, hinting that gut microbes may be playing a crucial role in the process.

How do gut bacteria influence fatty liver development?

The study found that the combination of low testosterone and fructose intake altered the composition of gut microbiota.

 

These microbial changes led to higher levels of pyruvate, a key molecule involved in cellular energy metabolism, in the intestine. Under certain conditions, it can be converted into substances that contribute to fat production in the liver.

 

The researchers discovered that pyruvate and fructose together promoted neutral lipid accumulation in liver cells.

What could these findings mean for human health?

Although the study was conducted in mice, it provides important clues about how hormonal changes and diet might interact in humans.

 

Low testosterone levels are common in ageing men and can also occur due to obesity, chronic illness, or lifestyle factors. When combined with high sugar consumption, the risk of liver fat accumulation may increase.

 

The findings also highlight the growing importance of the gut–liver axis, the biological communication between gut microbes and liver metabolism.

 

The researchers believe their work may open doors for future therapies targeting gut microbiota or metabolic pathways linked to pyruvate.