A hormone that triggers puberty and controls fertility in men could be developed as a treatment for non-alcoholic fatty liver disease, according to new research from Rutgers.
The study, published in the Clinical Investigation Journal, provides strong evidence that a modified version of the natural hormone kisspeptin can be used to treat non-alcoholic fatty liver disease (NAFLD). Globally, NAFLD is the most common form of chronic liver disease that affects children and adults and is linked to increases in obesity and type 2 diabetes.
NAFLD is known as a “silent” disease because it begins with few or no symptoms. It starts with the buildup of fat in the liver, leading to a condition known as “fatty liver.” As the disease worsens, the liver becomes inflamed, leading to 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 treatments to treat NASH.
The study’s lead researcher, Moshmi Bhattacharya, an associate professor in the Department of Medicine at Rutgers Robert Wood Johnson Medical School, has spent more than 15 years studying kisspeptin in health and disease. Kisspeptin, encoded by the KISS1 gene, was discovered in Hershey, Pennsylvania and named for the iconic Hershey chocolate “kisses”. In addition to playing a key role in pubertal development and maintenance of reproductive function, kisspeptin has also been linked to appetite and sexual attraction.
Bhattacharya along with co-author Andy Babwah, associate professor of pediatrics at Rutgers Robert Wood Johnson Medical School, initiated this study to decipher the roles of kisspeptin in the liver, in healthy and obese conditions. The study’s first author, Stephania Guzman, holds a Ph.D. candidate for the Rutgers Molecular Biosciences Graduate Program. This collaborative study also included researchers led by Waljit Dhillo at Imperial College London, UK.
Researchers fed mice a ‘Western’ diet high in fats and sugars to induce obesity and NAFLD. The study showed that kisspeptin given to these mice protected them from developing fatty liver disease, NASH and fibrosis. Kisspeptin works by binding to its receptor, a protein called KISS1R. The study also showed that when KISS1R is deleted from liver cells, kisspeptin cannot work and mice on a Western diet develop fatty liver disease. These experiments reveal a powerful relationship between kisspeptin and the reduction of liver fat and fibrosis.
The study found:
- Kisspeptin helps reduce fatty deposits in the liver and reverse more advanced disease.
- The mechanism by which kisspeptin works in the liver is now understood.
- Kisspeptin blood levels change in human NAFLD patients and in a mouse model of NAFLD.
“This work shows that the kisspeptin receptor signaling pathway has a potential therapeutic role in NAFLD,” said co-author Vinod K Rustgi, director of hepatology and emeritus professor of medicine at 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 positively impact the health and lives of millions of patients. in the world.”