New insights on molecular and epigenetic mechanisms of adipose browning in early cold exposure: focus on Zic1 expression regulation.

Adipocyte differentiation is regulated by the expression of lineage-specific transcriptional regulators and by epigenetic changes at distinctive developmental stages, which collectively generate a unique chromatin landscapes able to regulate the transcriptional program driving differentiation. Thus, the identification of essential transcriptional regulators and molecular mechanisms which are involved in brown and beige adipocyte development and their thermogenic function represents one of the major issue in the field of adipose tissue biology. With the aim to provide further clues on molecular mechanisms of browning, we evaluated the expression of some functional brown markers, with a specific focus on Zic1, in the early stages of cold exposure. Epigenetic regulations are investigated to elucidate potential mechanisms involved in Zic1 re-expression during cold-exposure in inguinal adipose tissue that is the adipose depot most prone to white-to-brown transdifferentiation. The differential gene expression pathway identified as soon as after 6h of cold exposure suggests that molecular mechanisms are triggered not only by chronic but also acute cold exposure. Interesting, variations in Zic1 expression and its epigenetic regulation have also been identified, demonstrating that further understanding of the role of epigenetic in these processes could provide relevant knowledge on non-shivering thermogenesis induction and its application in obesity prevention and therapy.