The use of marine animals as model systems to study fundamental biomedical processes has a rich history. For example, every undergraduate of Biology learns about the role of the squid giant axon in providing insights into how nerve cells work. A small northern fish, the rainbow smelt produces glycerol which serves as an antifreeze and allows smelt to live at winter temperatures where otherwise they would perish. Levels of glycerol in smelt (greater than 250 mM) are more than 1000 times higher than in humans. As such, smelt present a uniquely informative model for the study of glycerol synthesis. This area of metabolism is important to understand as glycerol, a small carbohydrate, forms the structural backbone to large fat (lipid) molecules. Drugs used to control type-2 diabetes, known as trizolidinedones, act by reducing the synthesis of glycerol and through a complex route to reduce the level of lipid in blood which in turn allows insulin to work better. We will use the high rates of glycerol production in smelt liver to reveal additional sites of metabolic control. This information will provide a context in which to probe sites of regulation of glycerol production in mammals and to develop pharmacological interventions to modify metabolism.