A new study from the Oklahoma Medical Research Foundation has found a potential cause of fatty liver disease, a condition linked to obesity that can lead to cirrhosis of the liver and an increased risk of liver cancer.
In a study published in the November issue of the Journal of Clinical Investigation, OMRF scientist Lijun Xia, M.D., Ph.D., and his research team uncovered evidence that a mix-up between the blood and lymph vessel systems in the small intestines causes deposits of fat in the liver, leading to a condition that resembles the most common form of liver disease in Western countries.
Xia’s research team focused on the function of a particular sugar—O-glycan—in the circulatory system. Studying mice that had been raised so that they lacked the gene that makes the sugar, the OMRF researchers found that the animals developed miswired blood and lymph systems. The miswired vessels caused problems in distribution of dietary fats throughout the systems, leading to an enlarged and fatty liver—the equivalent of the human illness known as non-alcoholic fatty liver disease.
“Before this, nobody knew what this sugar did in the system,” said Xia. “By taking the gene out of the vascular system, we found out how important this sugar is to the development of the circulatory system. Without it, the animals cannot live.”
The fused lymphatic and blood vessel systems sent fats from the small intestines directly to the liver. In healthy people, dietary fats are absorbed and transported by the lymphatic system to blood circulation, where the fats are distributed to various tissues for metabolism. Normally, only a small amount of fat leftovers reach the liver for further metabolism. But when a large amount of fat is sent through the hybrid blood-lymphatic system directly to liver, it can overload the liver, which is deadly.
The same hybrid system could be developing in humans, Xia said, possibly caused by poor diet. Diet is essential to intestinal bacteria, which are known to regulate new vessel formation in intestines. Because the small intestines are constantly replenishing themselves and regrowing cells, he suspects a poor diet could result in a lack of the proper bacteria and a mix-up in the lymphatic and blood vessel systems.
“We think what may be happening is that an abnormal diet could cause abnormal bacteria in the intestines, which could cause abnormal blood and lymph vessel growth in the small intestines,” he said. “We need to study and see if this is one of the causes of fatty liver disease in humans so we can find out how to stop it from happening.”
According to the Center for Disease Control, non-alcoholic fatty liver disease could affect as much as a quarter of the world’s population. The condition results from the accumulation of triglycerides in the liver and is associated with metabolic disorders such as insulin resistance, obesity, diabetes and high cholesterol—many of the conditions that contribute to heart disease. It can also lead to liver inflammation, cirrhosis and liver cancer.
Xia said Oklahomans should be worried, because as one of the states with the highest obesity rate, fatty liver disease is more common here and is a growing concern for overweight children.
“It’s a silent killer,” he said. “Even when the liver is half-full of fat, there may be no symptoms. So when a person finally begins to feel the effects of the disease, it’s often too late to help.”
Xia’s work was funded through grants from the National Heart, Lung and Blood Institute and the National Center for Research Resources. The research was an international effort, including Xia’s research team of Dr. Jianxin Fu, Michael McDaniel, Xiaowei Liu, and Sam McGee, OMRF imaging expert Dr. Florea Lupu and scientists from the Cancer Research UK London Research Institute, the Emory University School of Medicine, Katholieke Universiteit Leuven in Belgium, and the Boston University School of Medicine.
About Fatty Liver Disease
Based on estimates from the Center for Disease Control, non-alcoholic fatty liver disease could affect as many as 900,000 Oklahomans. The condition results from the accumulation of triglycerides in the liver and is associated with metabolic disorders such as insulin resistance, obesity, diabetes and high cholesterol—many of the conditions that contribute to heart disease. It can also lead to liver inflammation, cirrhosis and liver cancer.
OMRF (omrf.org) is an independent, nonprofit biomedical research institute dedicated to understanding and developing more effective treatments for human disease. Chartered in 1946, its scientists focus on such critical research areas as Alzheimer’s disease, cancer, lupus and cardiovascular disease.