Regulation of alcohol intake by fibroblast growth factor 21

In most regions of the world, people consume alcohol. Alcohol consumption is a major contributor to global disease and a leading cause of preventable death. Excessive alcohol consumption can lead to Alcohol Use Disorder (AUD). AUD is commonly referred to as alcoholism and alcohol abuse in culture and media. AUD is characterized by strong urges to drink, loss of control over the amount of alcohol consumed, and negative feelings when alcohol is not available. It is the most common substance use disorder in the world. Nearly one-third of American adults have experienced AUD at some point in their lives. Despite the high prevalence, there are not very many great therapeutic options available.

My project seeks to understand the role of fibroblast growth factor 21 (FGF21) in alcohol consumption. The hormone FGF21 is produced in the liver when someone drinks alcohol. When FGF21 is administered in higher doses, it signals to the brain to lower alcohol intake. We found that FGF21 works through a specific pathway in the brain, from one area called the basolateral amygdala (BLA) to another area called the nucleus accumbens (NAc) to lower alcohol intake. By using unique brain labeling strategies and genetically altered mice, we show that FGF21 acts on a particular type of brain cell (Vglut1 neurons), and that FGF21 signaling to these cells is necessary for FGF21 to lower alcohol use. Additionally, we found that some of these cells in the BLA connect directly to other cells in the NAc that are involved in controlling drinking behavior.