Insulin resistance and epigenetic regulation: insights from human studies and prospects for future research.

S.SOOKOIAN; T FERNÁNDEZ GIANOTTI; AL BURGUEÑO; CJ PIROLA

BioMolecular Concepts

Walter de Gruyter

Lugar: BERLIN; Año: 2011 vol. 2 p. 445 - 457

1868-5021

In this study, we review the current knowledge and recentinsights on the role of epigenetic factors in the developmentof human insulin resistance (IR)- and metabolic syndrome(MS)-related phenotypes, and attempt to lay a frameworkto consider IR as a potentially reversible incapacity to controlmetabolic homeostasis that is strongly infl uenced by theinterplay between external and internal cues. We summarizethe evidence on how tissue-specifi c epigenetic markers participateeither by activating or repressing the gene expressionprograms to modulate IR- and MS-associated traits. Someadditional data are provided about how the exploration ofDNA methylation markers in peripheral blood mononuclearcells potentially offers appealing information about the impactof epigenetics in the pathogenesis of IR. Clues about the relationbetween IR and impaired intrauterine growth explainedby fetal metabolic programming and epigenetic modifi cationsare shown, including novel fi ndings about the impact of histonemodifi cations. For instance, we observed that specifi cepigenetic factors in genes associated with mitochondrialbiogenesis may be associated with birth weight. Furthermore,some prospective ideas about the functional consequencesof genetic variation modulated by allele-specifi c epigeneticmarkers and its impact on MS susceptibility are also illustrated.Finally, we summarize the current knowledge of epigeneticsas the biological rationale for potential therapeuticintervention in IR and MS.