Abstract:
BACKGROUND:Obesity is a particularly complex disease that at least partially involves genetic and environmental perturbations to gene-networks connecting the hypothalamus and several metabolic tissues, resulting in an energy imbalance at the systems level. RESULTS:To provide an inter-tissue view of obesity with respect to molecular states that are associated with physiological states, we developed a framework for constructing tissue-to-tissue coexpression networks between genes in the hypothalamus, liver or adipose tissue. These networks have a scale-free architecture and are strikingly independent of gene-gene coexpression networks that are constructed from more standard analyses of single tissues. This is the first systematic effort to study inter-tissue relationships and highlights genes in the hypothalamus that act as information relays in the control of peripheral tissues in obese mice. The subnetworks identified as specific to tissue-to-tissue interactions are enriched in genes that have obesity-relevant biological functions such as circadian rhythm, energy balance, stress response, or immune response. CONCLUSIONS:Tissue-to-tissue networks enable the identification of disease-specific genes that respond to changes induced by different tissues and they also provide unique details regarding candidate genes for obesity that are identified in genome-wide association studies. Identifying such genes from single tissue analyses would be difficult or impossible.
journal_name
Genome Bioljournal_title
Genome biologyauthors
Dobrin R,Zhu J,Molony C,Argman C,Parrish ML,Carlson S,Allan MF,Pomp D,Schadt EEdoi
10.1186/gb-2009-10-5-r55subject
Has Abstractpub_date
2009-01-01 00:00:00pages
R55issue
5eissn
1474-7596issn
1474-760Xpii
gb-2009-10-5-r55journal_volume
10pub_type
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