Disruptions in a protein folding process happening in the brain, known as endoplasmic reticulum (ER) stress, can cause non-alcoholic fatty liver disease, independent of other variables. A research team at the George Washington University (GW) published their results in the Journal of Clinical Investigation Insight.
“Nearly 75 percent of obese adults experience non-alcoholic fatty liver disease. However, its underlying causes are unclear,” said Colin Young, Ph.D., senior author and assistant professor of pharmacology and physiology at the GW School of Medicine and Health Sciences. “Recent findings have pointed to ER stress as central to its development. What our research shows is that ER stress in the brain is a key contributor.”
As the primary site of cellular protein folding, the ER plays a critical role in maintaining cellular function. When there is nutritional excess, the protein load exceeds the ER folding capability and a collection of conserved signaling pathways, termed the unfolded protein response (UPR), are activated to preserve ER function. While valuable in the short-term, continual UPR activation, known as ER stress, is a leading pathological mechanism in metabolic disease, including obesity.
Young’s research team demonstrated that UPR activation in the brain, particularly in the forebrain, is causally linked to non-alcoholic fatty liver disease. Also known as hepatic steatosis, the research shows that brain ER pressure can cause the disease independent of changes in food consumption, body weight, and other factors.
Non-alcoholic fatty liver disease impairs normal liver function and is linked to other diseases including diabetes and cardiovascular disease. The following thing to do would be to discover the way it causes fat develop in the liver and how and why ER anxiety happens in the mind.
“Further research may give us another possible avenue for targeting fatty liver disease,” said Young. “The field has been focused on how we can improve the liver, for example, by developing drugs that target the liver. Our research suggests that we may also need to think about targeting the brain to treat non-alcoholic fatty liver disease.”