A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology

To describe tissue-specific functions, Recon 1 was tailored to describe metabolism in three human cells: adipocytes, hepatocytes, and myocytes. These cell-specific networks were manually curated and validated based on known cellular metabolic functions. To study intercellular interactions, a novel multi-tissue type modeling approach was developed to integrate the metabolic functions for the three cell types, and subsequently used to simulate known integrated metabolic cycles. In addition, the multi-tissue model was used to study diabetes: a pathology with systemic properties. High-throughput data was integrated with the network to determine differential metabolic activity between obese and type II obese gastric bypass patients in a whole-body context.The multi-tissue type modeling approach presented provides a platform to study integrated metabolic states. As more cell and tissue-specific models are released, it is critical to develop a framework in which to study their interdependencies.Metabolism has been implicated in most major human diseases including obesity, diabetes, cancer, and heart disease [1]. Thus, metabolism has been a field of study integral to many branches of medicine. In particular, obesity, a leading preventable cause of death, increases the likelihood of heart disease and diabetes, and represents one of the most serious current public health care problems [2]. Studying and understanding such systemic diseases however requires a fundamental and comprehensive analysis of not only the individual tissues and cell types, but also their integrated functions and interlinked interactions. Accurate physiological representation and analysis of systemic diseases however cannot be achieved unless an integrated multilevel and comprehensive modeling approach is undertaken and the appropriate computational infrastructure is fully developed and utilized.Genome-scale metabolic network reconstructions have been shown to provide an appropriate context for analyzing