In a new study, researchers have found a biomarker in humans tied to the development of Nonalcoholic Fatty Liver Disease that might help doctors detect early stages of the disease.
The research was conducted by a team at Joslin Diabetes Center, Harvard Medical School.
Fatty liver disease not associated with alcohol consumption, which is called Nonalcoholic Fatty Liver Disease or NAFLD, affects more than one billion people worldwide.
Even in children, the numbers are overwhelming, with up to 80% of pediatric patients who are considered obese affected worldwide.
People with NAFLD can progress to a severe form known as nonalcoholic steatohepatitis (NASH), which puts patients at higher risk for cirrhosis or liver cancer.
With no definitive treatment options or early detection methods yet discovered, researchers have been hard at work to identify early biomarkers of this disease.
In the study, the team determined that this biomarker, a protein known as “neuronal regeneration related protein” (or NREP), plays a significant role in the regulation of a pathway that is currently being reviewed in clinical trials as a treatment option for the disease.
They identified NREP as a new biomarker for NAFLD that is involved in the regulation of liver fat metabolism and in a process called fibrosis that occurs during the progression of the fatty liver disease that may lead to cirrhosis and liver cancer.
Previous studies had indicated genetics played a large role in who got NAFLD. But other evidence suggests that environmental factors such as parental health status are also at play.
The team tested this hypothesis first in animal models in their recently published study.
They used two groups of mice; one group had a genetic modification to have the markers of metabolic syndrome. Another group was not genetically modified.
They studied the offspring from these groups in three different categories: either one of the parents had metabolic syndrome, both parents did, or neither did.
Then they selected genetically normal offspring from each of these parents and fed them either a normal diet or a high caloric diet rich in fat to mimic obesity, and monitored their development.
When they looked in more depth at where the body fat accumulated, they saw a striking increase of fat in the liver. These offspring also had increased cholesterol and triglycerides in the liver.
They took a deep dive into the genetic pathways that were active in the healthy offspring versus the offspring that developed NAFLD.
They noticed the protein NREP was reduced in the unhealthy offspring. This was the first time NREP was linked to liver metabolism.
They then either increased (e.g. overexpressed) or decreased (e.g. knocked down) NREP in culture dishes to study this newly discovered function.
They wanted to see if this association of lower levels of NREP with NAFLD was also true in humans.
They collaborated with researchers in Finland who had a large database of information from patients in various stages of the liver disease to better understand the correlation with NREP levels.
They found as soon as NAFLD started, NREP circulating levels got lower, suggesting NREP is an early biomarker of NAFLD.
The discovery of NREP’s role in NAFLD not only yields a useful biomarker for tracking disease course, it can also help further the development of a treatment.
They hope in the clinic, this protein can be used as a biomarker to identify those individuals in that risk window.
The lead author of the study is Rohit N. Kulkarni, MD, Ph.D., Section Head, Senior Investigator, Islet Cell and Regenerative Biology.
The study is published in the Journal of Clinical Investigation.
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