Recent research conducted by Dr, Elif Oral has discovered that leptin therapy may be a viable treatment for nonalcoholic steatohepatitis (NASH), which is a form of fatty liver disease. Dr. Oral has been investigating leptin’s role in NASH and lipodystrophy since 2002. She has remained committed for nearly twenty years and now discovered that leptin therapy could reverse the damage done by NASH.
Nonalcoholic steatohepatitis is characterized by an accumulation of fat in the liver that results in inflammation and liver damage. It impacts those who drink very little or not at all. If left untreated, it can lead to cirrhosis and liver failure, mimicking the disease that affects heavy drinkers. NASH sees symptoms like jaundice, weakness, fatigue, itching, swelling in the legs and abdomen, mental confusion, weight loss, loss of appetite, nausea, vomiting, abdominal pain, and spider-like blood vessels. All of these effects are the result of a buildup of fat, but doctors are unsure as to why this occurs. They have only identified a number of risk factors: type 2 diabetes, obesity, metabolic syndrome, and high cholesterol. Because these are the only understood contributing factors, they also influence treatment. Doctors will suggest that one loses weight, avoids alcohol, maintains a healthy diet and exercise schedule, controls diabetes, and lowers cholesterol.
Leptin and NASH
Dr. Oral’s research focused on leptin, a hormone that plays a role in curbing appetite and stopping weight gain, and its connection to NASH. She investigated this hormone and its effects on NASH patients both with and without partial lipodystrophy, which is a rare, genetic condition that causes patients to contain fat in the upper bodies but not in their extremities.
Through three studies, Dr, Oral was able to demonstrate that leptin is necessary for regulating the deposition of fat in the liver. She also proved that it is able to reverse this activity and rid the liver of that fat, therefore treating NASH.
About the Trials
Two, open-label trials were conducted, in which 32 patients were enrolled. Nine patients were male and only presented with NASH and low leptin levels, while the remaining 23 participants had both NASH and partial lipodystrophy. These people were chosen based on research that showed 35-40% of them had low leptin levels, therefore making them the ideal study candidates. All patients were given leptin therapy, metreleptin, for one year.
The research team performed blind, paired liver biopsies, which demonstrated that fat in the liver had been reduced after the year of treatment. The biopsies also revealed lower NASH scores, improved body weight, and better insulin sensitivity.
While this research is only in regard to leptin, Dr. Oral believes that other treatments could be formulated to activate leptin, therefore providing more therapeutic options for patients.
This research is very exciting, as it illustrates the potential of leptin therapy as a treatment for NASH. It is important to note that it is not a solution for obese patients, as leptin is already found in high amounts in these people. In fact, these levels can even be causative of NASH. While this therapy is not viable for obese patients, Dr. Oral believes that it could be useful for those in the early overweight category.
Further research must be conducted, but this data is very promising for leptin therapy as a treatment for NASH. You can find the source article here.