The Transcription Factor : Novel Insights into Metabolic Diseases and Adipose Tissue Dysfunction.

The transcription factor , from the gene family, has long been studied due to its critical role in physiological activities in normal cells, such as organ development and body patterning, and pathological activities in cancer cells. Nonetheless, recent evidence supports the hypothesis of a role for in metabolic diseases, particularly in obesity and type 2 diabetes (T2D). In line with the current opinion that adipocyte and adipose tissue (AT) dysfunction belong to the group of primary defects in obesity, linking this condition to an increased risk of insulin resistance (IR) and T2D, the gene has been shown to regulate adipocyte function and AT remodeling both in humans and mice. Epigenetics adds complexity to gene regulation in metabolic diseases. Indeed, epigenetic mechanisms, specifically DNA methylation, influence the dynamic expression profile. In human AT, the DNA methylation profile at the gene is associated with hypertrophic obesity and an increased risk of developing T2D. Thus, an inappropriate gene expression may be a mechanism causing or maintaining an impaired AT function in obesity and potentially linking obesity to its associated disorders. In this review, we integrate the current evidence about the involvement of in regulating AT function, as well as its association with the pathogenesis of obesity and T2D. We also summarize the current knowledge on the role of DNA methylation in controlling expression. Moreover, considering the susceptibility of epigenetic changes to reversal through targeted interventions, we discuss the potential therapeutic value of targeting DNA methylation changes in the treatment of metabolic diseases.