Bastarrachea RA, López-Alvarenga JC, Comuzzie AG

Language: Spanish
References: 30
Page: 112-120
PDF size: 104.22 Kb.

ABSTRACT

The cellular mechanisms linking obesity and atherosclerosis are complex and have not been fully elucidated. Concerning a possible molecular link between atherosclerosis, endothelial function, insulin resistance, and obesity, the research has focused on questions looking for a molecular link between lipid metabolism, insulin action, and adipose tissue metabolism at a genomic regulatory level. Among the fat- derived adipokines, adiponectina, CRP (C-reactive protein) and IL-6 are the most strongly molecules associated with increased cardiovascular risk. Obesity and atherosclerosis are associated with a state of abnormal inflammatory response. The state of chronic inflammation occurs at metabolically relevant sites, such as the liver, muscle, adipose tissue and the endothelium. The abnormal production of TNF-a in obesity is a paradigm for the metabolic significance of this inflammatory response. Alterations in the structure, function and regulation of transcription factors appear to be such signalling steps which might play an essential role in the pathogenesis of atherosclerosis associated with obesity and the metabolic syndrome. Recent examples are members of the nuclear hormone receptor superfamily, eg peroxisome proliferator-activated receptor (PPAR) isoforms and the nuclear transcription factor-kappaBeta (NF-kß). Beside their regulation by different metabolites, these transcription factors are also targets of hormones, like insulin and leptin, growth factors, and inflammatory signals. Major signalling pathway coupling receptors at the cell surface for hormones, growth factors as well as cytokines to gene regulatory events in the nucleus are the MAP-kinase (MAPK) cascades. There is no doubt that future research on these cell surface coupling receptors and nuclear transcription factors will provide a broader view of the link between excessive adiposity and atherosclerosis.

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