FGF21

FGF21 is a hepatokine, a hormone secreted primarily by the liver as shown by the Potthoff lab. Among other activities, FGF21 regulates simple sugar intake and preferences for sweet foods via signaling through FGF21 receptors in the hypothalamus and correlates with reduced dopamineneurotransmission within the nucleus accumbens. The Potthoff lab followed up on their discovery and later revealed that FGF21 signaling to the ventromedial hypothalamus suppresses sugar intake by enhancing the activity of glucose-excited and glucose-inhibited neurons in response to high, but not low, glucose levels. The Potthoff lab was also the first to demonstrate that FGF21 has direct actions on adipose tissues, where it can increase acute insulin sensitivity and glucose uptake. Initially thought of as a starvation hormone, FGF21 is now described as "an endocrine mediator of the intracellular stress response to various nutritional manipulations, including excess sugars and alcohol, caloric deficits, a ketogenic diet, and amino acid restriction".