When
3:30 – 4:30 p.m., March 27, 2025
Presenter:
Dr. David J. Mangelsdorf, Professor and Chair
Department of Pharmacology, University of Texas Southwestern Medical Center
Image
Fibroblast growth factor 21 (FGF21) is an endocrine and paracrine factor that is produced in response to nutrient and metabolic stress and is known to have diverse roles in maintaining lipid and glucose homeostasis. In both animals and humans, the most potent inducer of circulating FGF21 is alcohol consumption, a finding that is supported by human genetic studies. In response to alcohol, FGF21 is made and released from the liver into circulation, and then enters discrete brain regions where it acts to suppress further alcohol intake, increase drinking pure water, and decrease alcohol-induced sedation. Loss of FGF21 or its receptor makes animals more prone to increased alcohol intake, dehydration, and inebriation. Pharmacologic administration of FGF21 greatly enhances both its anhedonic and amethystic properties by reversing the desire to consume alcohol and markedly reversing the intoxication of drunk mice. The diverse actions of FGF21 are mediated through a unique receptor complex that is composed of a classic FGF receptor and an essential co-receptor, b-Klotho. Investigation into the CNS regions required for FGF21’s effects has revealed the existence of complex neural endocrine circuits, which in addition to regulating metabolism, also govern reward behaviors and arousal in response to alcohol.
Hosted by: Dr. Thomas Tomasiak