According to their findings, a specific strain of good cholesterol -- high-density lipoprotein (known as HDL or HDL3) -- may protect the liver from damage and reduce the risk of liver disease. When HDL3 is produced by the intestines, it blocks harmful bacteria that can enter the liver and increase the risk for disease.
“Even though HDL has been considered ‘good cholesterol,’ drugs that increase overall HDL levels have fallen out in favor in recent years because of clinical trials that showed no benefit in cardiovascular disease,” said researcher Gwendalyn J. Randolph, Ph.D. “But our study suggests that raising levels of this specific type of HDL, and specifically raising it in the intestine, may hold promise for protecting against liver disease, which, like heart disease, also is a major chronic health problem.”
Promoting better liver function
The researchers explained that they began working in this area to study necrotizing enterocolitis -- a bowel condition common in infants in which the intestines become inflamed. In some cases, the intestines may need to be removed, and that can lead to an increased risk of liver damage. The team began working on mice to determine how inflammation in the intestines may impact the liver and what role HDL plays in combating these health risks.
They explained that inflammation directly causes intestinal issues that lead to liver damage. Lipopolysaccharides are inflammatory molecules that have the ability to reach the liver through the body’s portal vein and ultimately increase the risk of liver disease and fibrosis. Prior to this study, it was unclear how HDL would interact with lipopolysaccharides or if it was able to enter the portal vein.
“There were hints in the literature that HDL might interfere with lipopolysaccharide’s detection by immune cells and that the receptor for lipopolysaccharides might be linked to liver disease following the bowel surgery,” said Dr. Randolph. “However, no one thought HDL would directly move from the intestine to the liver, which requires that it enter the portal vein. In other tissues, HDL travels out through a different type of vessel called a lymphatic vessel that, in the intestine, does not link up to the liver.”
The researchers found that HDL3 has a direct route from the intestine to the portal vein. From there, it works to counteract harmful inflammatory proteins. Going forward, the researchers plan to keep working towards creating drugs that can mimic what HDL3 does so that long-term liver damage can be prevented.
“We are hopeful that HDL3 can serve as a target in future therapies for liver disease,” said Dr. Randolph.