Regulation of glycogen in health and disease

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Project Summary/Abstract 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. In hepatocytes, glycogen triggers lipogenesis via changes in the AMPK pathway; while in adipocytes glycogen turnover is crucial for thermogenic responses in response to cold. We will explore these hypotheses with two aims that focus on these crucial pathways in liver and fat cells, hoping to develop new approaches to therapies for these devastating diseases.