Brain Plays Key Role in Alcoholic Fatty Liver Disease

A new study has found that mice lacking a certain adenosine receptor (A2B) do not develop hepatic steatosis (fatty accumulation in the liver) despite binge-like alcohol consumption. The study is published ahead of print in the American Journal of //Physiology—Endocrinology and Metabolism. The fatty accumulation can lead to impairment of liver function and increase the risk for liver cancer. Alcohol-induced hepatic steatosis occurs slowly in response to chronic alcohol abuse. However, it can also occur in response to large quantities of alcohol consumed in individual short bouts such as binge drinking. Binging on alcohol can change the ability of the liver and fat tissue to metabolize fatty acids, leading to fat accumulation. Binge-like alcohol consumption also increases bodily levels of adenosine—a chemical that regulates the electrical activity of brain cells called neurons. This increase has been associated with the development of liver disease.

Alcohol also stimulates the activity of neurons that express Agouti-related protein (AgRP) and increases their expression of AgRP. AgRP neurons in a brain region called the hypothalamus coordinate body weight regulation (including the overeating that often occurs with heavy drinking) and control the autonomic nervous system, which plays a role in regulating liver function.

In this new study, researchers explored the dual roles of the A2B receptor and AgRP in the development of liver fat buildup in response to binge-like alcohol consumption in mice. The research team studied multiple groups of mice, including:

one group lacking AgRP,

a second group lacking the A2B receptor in the brain, and

a third group lacking the A2B receptor only in its AgRP neurons.

Advertisement

These groups were compared with appropriate controls that had these proteins properly expressed. All animals were given either alcohol or a sweetened, calorically matched nonalcoholic beverage. The group lacking AgRP had reduced overall fat accumulation, including triglycerides, in the liver following binge-like alcohol consumption. By contrast, the loss of A2B receptors in the central nervous system increased alcohol-induced liver fat accumulation, although eliminating A2B receptors only in AgRP neurons was not sufficient to reproduce this finding.

By highlighting the ability of the brain to respond to alcohol through internal signals, including adenosine and AgRP, this work may potentially reveal new targets that may help curb liver damage associated with alcohol excess.

Advertisement

Source-Newswise