Understanding Metabolic Regulation at a Systems Level: Metabolite Sensing, Mathematical Predictions, and Model Organisms

UMMS Affiliation

Program in Systems Biology; Program in Molecular Medicine

Publication Date


Document Type



Biochemistry | Cellular and Molecular Physiology | Systems Biology


Metabolic networks are extensively regulated to facilitate tissue-specific metabolic programs and robustly maintain homeostasis in response to dietary changes. Homeostatic metabolic regulation is achieved through metabolite sensing coupled to feedback regulation of metabolic enzyme activity or expression. With a wealth of transcriptomic, proteomic, and metabolomic data available for different cell types across various conditions, we are challenged with understanding global metabolic network regulation and the resulting metabolic outputs. Stoichiometric metabolic network modeling integrated with "omics" data has addressed this challenge by generating nonintuitive, testable hypotheses about metabolic flux rewiring. Model organism studies have also yielded novel insight into metabolic networks. This review covers three topics: the feedback loops inherent in metabolic regulatory networks, metabolic network modeling, and interspecies studies utilizing Caenorhabditis elegans and various bacterial diets that have revealed novel metabolic paradigms.


Caenorhabditis elegans, feedback loop, flux balance analysis, gene regulation, homeostasis, metabolic network

DOI of Published Version



Annu Rev Genet. 2015 Nov 23;49:553-75. doi: 10.1146/annurev-genet-112414-055257. Link to article on publisher's site

Journal/Book/Conference Title

Annual review of genetics

Related Resources

Link to Article in PubMed

PubMed ID