Glycerol and Glycerol-3-Phosphate: Multifaceted Metabolites in Metabolism, Cancer, and Other Diseases

Glycerol and glycerol-3-phosphate (Gro3P) are key metabolites at the intersection of carbohydrate, lipid, and energy metabolism. Their production and usage are organismal and cell-type specific. Glycerol has unique physicochemical properties enabling it to function as an osmolyte, protein structure stabilizer, and an antimicrobial and antifreeze agent, important to the preservation of many biological functions. Glycerol and Gro3P are implicated in many physiological and disease processes relating to energy metabolism, thermoregulation, hydration, skin health, male fertility, aging, and cancer. Glycerol has countless applications in the food, pharmaceutical, and cosmetics industries. It is used as a sweetener, preservative, thickening agent, humectant, osmolyte, and cryoprotectant. It is widely used in skin and wound care products, laxatives, in cell and tissue preservation, and in medicines for numerous conditions. Here, we review the multiple uses and functions of glycerol and Gro3P and associated transporters, enzymes, and target genes in health, senescence, and disease. We discuss the evidence that glycerol may be present at much higher levels in tissues and cells than in the blood. We bring particular focus to the newly identified glycerol shunt in the direct formation of glycerol independent of lipolysis and as a pathway allowing cells to adapt to various stresses. Relevant to chronic metabolic diseases, cancer and aging, glycerol and Gro3P present important translational implications and thus warrant much more attention.