Metabolic Syndrome: From the Genetics to the Pathophysiology

SILVIA SOOKOIAN; CARLOS J. PIROLA

CURRENT HYPERTENSION REPORTS

CURRENT MEDICINE GROUP

Año: 2011 vol. 13 p. 149 - 157

1522-6417

Abstract The metabolic syndrome (MS) constitutes acombination of underlying risk factors for an adverseoutcome, cardiovascular disease. Thus, the clinical behaviorof the MS can be regarded as a whole. Nevertheless, from apathogenic point of view, understanding of the underlyingmechanisms of each MS intermediate phenotype is farbeyond their understanding as an integrative process.Systems biology introduces a new concept for revealingthe pathogenesis of human disorders and suggests thepresence of common physiologic processes and molecularnetworks influencing the risk of a disease. This papershows a model of this concept to explain the geneticdeterminants of MS-associated phenotypes. Based on thehypothesis that common physiologic processes and molecularnetworks may influence the risk of MS diseasecomponents, we propose two systems-biology approaches:a gene enrichment analysis and the use of a protein-proteininteraction network. Our results show that a network drivenby many members of the nuclear receptor superfamily ofproteins, including retinoid X receptor and farnesoid Xreceptor (FXR), may be implicated in the pathogenesis ofthe MS by its interactions at multiple levels of complexitywith genes associated with metabolism, cell differentiation,and oxidative stress. In addition, we review two alternativegenetic mechanisms that are gaining acceptance in thephysiopathology of the MS: the regulation of transcriptionaland post-transcriptional gene expression by microRNAsand epigenetic modifications such as DNA methylation