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

Aarash Bordbar, Adam M Feist, Renata Usaite-Black, Joseph Woodcock, Bernhard O Palsson, Iman Famili
2011 BMC Systems Biology  
Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconstructed allowing the systems analysis of human metabolic physiology and pathology. Utilizing highthroughput data, Recon 1 has recently been tailored to different cells and tissues, including the liver, kidney, brain, and alveolar macrophage. These models have shown utility in the study of
more » ... stems medicine. However, no integrated analysis between human tissues has been done. Results: 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. Conclusion: 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.
doi:10.1186/1752-0509-5-180 pmid:22041191 pmcid:PMC3219569 fatcat:xukpwre3wfbvtalggxnsui4xru