Researchers from the Karolinska Institute in Sweden have found a new molecular pathway for treating liver diseases. The molecular pathway when in silenced condition would be able to restore the normal functions of the immune system in the patients who have fatty liver disease.
The findings of the study suggest new strategies to treat the diseased condition as it a major risk factor for health in obese people. The study is published in the scientific journal Science Translational Medicine.
Non- alcoholic fatty liver disease (NAGLD) is a condition characterized by the deposition of extra fat in the liver. People who drink very little or no alcohol suffer from this disease. This condition is very common among obese or diabetic individuals. No medication exists in the market to treat non-alcoholic fatty liver disease.
During the study, researchers wanted to know the exact changes in the mechanism that occurs at the cellular and molecular level. The study used the rodent models and then compare the results with the human fatty liver. They tried many experiments to discover the pathway that could prove helpful in restoring the damage.
Scientists discovered that a type of white blood cell, important for the immune function, called macrophages gives a response to excess fat. Macrophages are involved in the burning of excess fat and they die doing so by producing a large number of oxidants which in return damage the liver.
Researchers showed through the investigation that an antioxidant protein known as NRF2 present in the body protects it from the injurious oxidants. The level of this antioxidant protein falls in the obese mice or patients.
Valerio Azzimato who is the first author of this study and a researcher at the Department of Medicine in Huddinge, Karolinska institute said that reduction in the level of antioxidant protein NRF2 reveals that obese people do not have the capacity to deal with the oxidative stress in the body due to fat deposition in the liver.
An elevated level of small non-coding RNA molecule or microRNA known as miR144 was found in the liver of obese mice and individuals. When the body undergoes oxidative stress, hepatocytes (most abundant cells in the liver and immune system) produce a high level of this particular miR144.
The antioxidant response becomes weaker when miR144 molecules induce changes in the NRF2 gene by lowering the level of protein in NRF2 molecules. Through using the technology that causes the silencing of some particular genes in the macrophages of the liver, scientists were able to decrease the expression of miR144 molecules in the immune cells.
The antioxidant activity of the liver was restored as it lowers the number of oxidant molecules in the liver. It normalized the link between the hepatocyte’s liver cells and macrophages. Myriam Aouadi who is a corresponding author of the study and a researcher at the Department of Medicine in Huddinge, Karolinska Institute said that if exogenous antioxidants were given to obese people, it produces long term side effects in many tissues.
Scientists believed that endogenous antioxidant response will increase by targeting miR144 molecules. And this proves to be an effective therapeutic strategy to treat liver disease in the people who are obese or who have non-alcoholic steatohepatitis disease as it becomes the major risk factor for liver cancer across the whole world. Currently, there is no medical treatment available in the market for this disease.