There is little doubt that we are in the midst of a worldwide epidemic of obesity, diabetes and fatty liver disease, and disruptions in energy balance are at the heart of these disorders. The first option for energy storage and utilization in metabolically active tissues such as liver, fat and muscle is glycogen. We propose that the regulation of glycogen metabolism is comprised of complex feedback and feedforward pathways, and as such, glycogen itself plays a major role in the overall control of energy disposition in liver and adipose tissue. Glycogen represents the first choice for energy storage and utilization in both tissues, but also serves as a modulator of metabolism in physiological and pathological states, directing the cell to utilize or store energy. We will explore this hypothesis with three aims: 1) We will investigate the molecular mechanisms whereby insulin controls glycogen synthesis; 2) We will evaluate the mechanisms and consequences of increased glycogen accumulation in obesity; and 3) We will evaluate the role of glycogen accumulation in sustaining low grade, chronic inflammation.
Obesity and Type 2 diabetes have reached epidemic proportions. We will investigate the molecular mechanisms by which glycogen serves a role as a master regulator of metabolism in physiological and pathological states.