@article {1198,
	title = {Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice.},
	journal = {Stress (Amsterdam, Netherlands)},
	year = {2016},
	month = {2016 Mar 7},
	pages = {1-11},
	abstract = {Chronic stress has been associated with obesity, glucose intolerance, and insulin resistance. We developed a model of chronic psychosocial stress (CPS) in which subordinate mice are vulnerable to obesity and the metabolic-like syndrome while dominant mice exhibit a healthy metabolic phenotype. Here we tested the hypothesis that the metabolic difference between subordinate and dominant mice is associated with changes in functional pathways relevant for insulin sensitivity, glucose and lipid homeostasis. Male mice were exposed to CPS for four weeks and fed either a standard diet or a high-fat diet (HFD). We first measured, by real-time PCR candidate genes, in the liver, skeletal muscle, and the perigonadal white adipose tissue (pWAT). Subsequently, we used a probabilistic analysis approach to analyze different ways in which signals can be transmitted across the pathways in each tissue. Results showed that subordinate mice displayed a drastic downregulation of the insulin pathway in liver and muscle, indicative of insulin resistance, already on standard diet. Conversely, pWAT showed molecular changes suggestive of facilitated fat deposition in an otherwise insulin-sensitive tissue. The molecular changes in subordinate mice fed a standard diet were greater compared to HFD-fed controls. Finally, dominant mice maintained a substantially normal metabolic and molecular phenotype even when fed a HFD. Overall, our data demonstrate that subordination stress is a potent stimulus for the downregulation of the insulin signaling pathway in liver and muscle and a major risk factor for the development of obesity, insulin resistance, and type 2 diabetes mellitus.},
	keywords = {Adipose tissue, insulin, IRS1, IRS2, metabolic syndrome, obesity, pathway analysis},
	issn = {1607-8888},
	doi = {10.3109/10253890.2016.1151491},
	url = {http://www.tandfonline.com/doi/abs/10.3109/10253890.2016.1151491?journalCode=ists20},
	author = {Sanghez, Valentina and Cubuk, Cankut and Sebasti{\'a}n-Leon, Patricia and Carobbio, Stefania and Dopazo, Joaquin and Vidal-Puig, Antonio and Bartolomucci, Alessandro}
}
@article {1005,
	title = {Genomics and transcriptomics in drug discovery.},
	journal = {Drug discovery today},
	volume = {19},
	number = {2},
	year = {2014},
	month = {2013 Jun 14},
	pages = {126-32},
	abstract = {The popularization of genomic high-throughput technologies is causing a revolution in biomedical research and, particularly, is transforming the field of drug discovery. Systems biology offers a framework to understand the extensive human genetic heterogeneity revealed by genomic sequencing in the context of the network of functional, regulatory and physical protein-drug interactions. Thus, approaches to find biomarkers and therapeutic targets will have to take into account the complex system nature of the relationships of the proteins with the disease. Pharmaceutical companies will have to reorient their drug discovery strategies considering the human genetic heterogeneity. Consequently, modeling and computational data analysis will have an increasingly important role in drug discovery.},
	keywords = {adverse effects, Drug discovery, drug repositioning, metagenomics, modeling, network analysis, pathway analysis},
	issn = {1878-5832},
	doi = {10.1016/j.drudis.2013.06.003},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/23773860},
	author = {Dopazo, Joaquin}
}
