(352c) Tissue-Specific Reconstructions of Mouse Metabolism and Interactions Among the Multi-Tissue Network

Genome-scale metabolic reconstruction of Mus Musculus was built on Homo sapiens Recon 1 and have since been utilized to integrate with or to reconstruct gene regulatory networks. With the huge amount of available high-throughput gene expression data for targeted organs/cells, the reconstruction of different tissue and cell-type specific metabolic models for mouse becomes possible. Such models are highly relevant to study diseases on a mechanistic basis and select potential drug targets. Our project utilized a highly efficient automated metabolic reconstruction technique (Automated Context Specific Reconstruction of Metabolic Models or ACREM) to tailor the generic mouse model to three tissue-specific (liver, adipose tissue and muscle) metabolic models. Besides passing the universal functional and consistency tests, these networks also describe metabolic tests unique to the tissue systems.

These networks were subsequently used to study insulin resistance and diabetes and obesity in the standard C57BL/6 mice. The glucose-fatty acid interaction in adipose, skeletal muscle and liver play crucial roles in insulin resistance and type II diabetes. The metabolic functions for three mouse tissues have been integrated to study intercellar interactions and describe different metabolic states.