Diseased livers in men undergo a ‘sex change’ as a defense mechanism

BRISBANE, Australia — Does a man’s liver get in touch with its feminine side to protect against disease? Scientists from Queensland University found that diseased livers in men actually experience a “sex change” — which may be part of a potential defense mechanism.

The notion of a male liver becoming female in response to disease certainly comes as a surprise to researchers. Study authors made the discovery while conducting an investigation into why bodily circadian clock disruptions have a link to obesity, type 2 diabetes, and numerous other liver diseases.

“When a high-fat diet was fed to mice that had their circadian clock gene turned off, we expected them to develop diabetes or non-alcoholic fatty liver disease (NAFLD) like the control mice, but they didn’t,” says Institute for Molecular Bioscience (IMB) lead researcher Frederic Gachon in a university release. “We also found that the liver of the obese male mice had been feminized probably due in part to the protective nature of the female sex hormone, estrogen.”

Circadian rhythm changes affect the hormones

Scientists consider the human liver sexually dimorphic, meaning male and female livers function in distinct ways metabolically. So, after observing these liver sex-swaps in mice, researchers turned their attention to human samples. Male human livers showed the same tendency to change genders in response to disease.

“The more advanced the disease, the more feminization we saw in the liver tissue,” Dr. Gachon explains. “It appears that the disruption of circadian rhythms might be protecting the liver by influencing the levels of hormones such as growth hormone, estrogen and testosterone.”

Each person’s internal body clock dictates biological functions such as sleep, metabolism, body temperature, and hormone secretion. Meanwhile, NAFLD is quite common, and affects roughly 100 million Americans. Men are at particularly higher risk of developing NAFLD, and a common symptom is sleep issues.

“This study suggests that the disruption of the circadian clock gives the body flexibility in metabolic pathways that can help to slow down disease progression,” Dr. Gachon concludes. “In light of these findings, we are investigating whether behavioral and hormonal interventions are possible treatments for liver disease.”

The study is published in Proceedings of the National Academy of Sciences.