Kisspeptin: A new drug for treatment of NAFLD

Globally, NAFLD is the most common form of chronic liver disease that affects children and adults and is linked to the rise in obesity and Type 2 diabetes.

Researchers have found in a new study that modified version of the naturally occurring hormone kisspeptin can be used to treat non-alcoholic fatty liver disease (NAFLD). Kisspeptin is a hormone that triggers puberty and controls fertility in humans. 

The research has been published in the  Journal of Clinical Investigation.

The study provides powerful evidence that a modified version of the naturally occurring hormone kisspeptin can be used to treat non-alcoholic fatty liver disease (NAFLD). 

NAFLD is known as a "silent" disease because it starts off with few or no symptoms. It begins with the accumulation of fat in the liver, resulting in a condition known as 'fatty liver'. 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.

Study lead investigator, Moshmi Bhattacharya, an associate professor in the Department of Medicine at the Rutgers Robert Wood Johnson Medical School, has spent over 15 years studying kisspeptin in health and disease. Kisspeptin, encoded by the KISS1 gene, was discovered in Hershey, Pa. and named for the iconic Hershey chocolate "kisses." In addition to playing key roles in pubertal development and maintaining reproductive function, kisspeptin has also been linked to appetite and sexual attraction.

Bhattacharya along with co-author Andy Babwah, an associate professor in pediatrics at Rutgers Robert Wood Johnson Medical School, initiated this study to decipher the roles of kisspeptin in the liver, under healthy and obese conditions. The study's first author, Stephania Guzman, is a Ph.D. candidate in Rutgers Molecular Biosciences Graduate Program. This collaborative study also included researchers led by Waljit Dhillo at the Imperial College London, U.K.

The researchers fed mice a high-fat, high-sugar 'Western' diet to induce obesity and NAFLD. The study showed that kisspeptin given to these mice protected them from the development of fatty liver, NASH and fibrosis. Kisspeptin works by binding its receptor, a protein called KISS1R. The study also showed that when KISS1R is deleted from liver cells, kisspeptin cannot function and mice on western diet develop fatty liver. These experiments uncover a powerful relationship between kisspeptin and the reduction of liver fat and fibrosis.

For further information, visit here:

10.1172/JCI145889