Glycogenin is dispensable for normal liver glycogen metabolism and body glucose homeostasis

Abstract

Glycogen is a glucose-storage polysaccharide molecule present in animals, fungi and bacteria. The enzyme glycogenin can self-glycosylate, forming an oligosaccharide chain that primes glycogen synthesis. This priming role of glycogenin was first believed to be essential for glycogen synthesis, but glycogen was then found in the skeletal muscle, heart, liver and brain of glycogenin-knockout mice (Gyg KO), thereby showing that glycogen can be synthesized without glycogenin. Within the liver, glycogen is present in the form of individual glycogen particles, called β particles, and larger composite aggregates of linked β particles, called α particles. Previous studies suggested that liver glycogenin plays a role in linking β particles into α particles and thus participating in glucose homeostasis, which implies that α particles would be absent in Gyg KO mice liver. Here we test this through targeted characterization of glycogen structure and through proteomic and metabolic studies on Gyg KO mice. The results show that, contrary to what had been believed, glycogenin is not necessary for normal liver-glycogen metabolism.