Transforming liver disease treatment with kisspeptin

Transforming liver disease treatment with kisspeptin
© iStock/Vladimir Borovic

Researchers have discovered that kisspeptin has therapeutic effects on non-alcoholic fatty liver disease in a mouse study.

The research team have made a potentially transformative discovery that could revolutionise non-alcoholic fatty liver disease (NAFLD) with a treatment that derives from kisspeptin, which is a hormone that triggers puberty and controls fertility in humans.

This study was published in the Journal of Clinical Investigation and carried out by study lead investigator, Moshmi Bhattacharya, an Associate Professor in the Department of Medicine at the Rutgers Robert Wood Johnson Medical School and co-author Andy Babwah, an Associate Professor in paediatrics at Rutgers Robert Wood Johnson Medical School.

What is non-alcoholic fatty liver disease?

NAFLD is a term that covers a range of conditions caused by a build-up of fat in the liver. This disease usually does not cause any harm in the early stages, however, if it progresses to serious liver damage, it can be life-threatening.

As the disease worsens, the liver becomes inflamed resulting in non-alcoholic steatohepatitis (NASH). This is followed by fibrosis and cirrhosis, where the liver becomes scarred and irreversibly damaged. A subset of NASH patients with cirrhosis will also develop liver cancer. Currently, there are no approved therapeutics to treat NASH.

There are several risk factors for NAFLD including obesity, type 2 diabetes, high blood pressure, and smoking.

Kisspeptin and its potential

To carry out their research, the team fed mice a high-fat, high-sugar ‘Western’ diet to induce obesity and NAFLD.  The mouse trial uncovered that kisspeptin protected the mice from the development of fatty liver, NASH, and fibrosis. Kisspeptin uniquely works by binding its receptor, which is a protein called KISS1R. Within the study, when KISS1R is deleted from liver cells, kisspeptin cannot function and the mice developed a fatty liver. This groundbreaking experience illuminates the powerful relationship between kisspeptin and the reduction of liver fat and fibrosis.

Most notably, the study revealed three main outcomes. The first outcome was that kisspeptin helped reduce fat deposited in the liver and reversed the more advanced disease. Secondly, the mechanism by which kisspeptin functions in the liver was understood, and the third outcome was that blood kisspeptins levels change in human NAFLD patients and a mouse model of NAFLD.

“This work shows the kisspeptin receptor signalling pathway has a potential therapeutic role in NAFLD,” concluded co-author, Vinod K Rustgi, Director of Hepatology and a Distinguished Professor of Medicine at the Rutgers Robert Wood Johnson Medical School. “It does this by protecting against the development of fat in the liver and reducing inflammation and fibrosis. As such, it has the potential to favourably impact the health and lives of millions of patients around the globe.”

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