Dna methylation and hepatic insulin resistance and steatosis.

SILVIA SOOKOIAN; CARLOS J. PIROLA

CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2012 vol. 15 p. 350 - 356

1363-1950

Purpose of review: In this review, we show novel evidence about the role of the liver in the development of insulin resistance (IR), and suggest that abnormal hepatic triglycerides accumulation is not an innocent bystander comorbidity but adversely affects the peripheral insulin sensitivity. Recent findings: The core of this review is built up around the concept that liver DNA methylation of the peroxisome proliferative activated receptor gamma coactivator 1 alpha (PPARGC1A) gene promoter modulates the status of peripheral IR and is strongly associated with plasma fasting insulin levels. We discuss about other mechanisms associated with PPARGC1A regulation, such as an acetylation/ deacetylation switch, and how these events impact on the liver metabolic function. We suggest a mitochondrial-centric approach to understand the connection between nonalcoholic fatty liver disease and IR. We finally show new data about how the liver epigenome is modulated by nutritional cues, and introduce the role of epigenetics in liver metabolic programming. Summary: The implications of these findings for clinical practice are promising, as the inherent plasticity of epigenetic modifications, produced either physiologically or pathologically, suggests that early therapeutic intervention in patients with fatty liver can potentially revert the systemic phenotype associated with IR.