In 2009, a new family of DNA modifying enzymes, the Tet-eleven translocation family was identified as 2-oxoglutarate (2-OG) and Fe(II)dependent dioxygenases. This family of enzymes comprises three proteins TET1, TET2 and TET3 that share a carboxyl-terminal core catalytic domain consisting of a conserved cysteine-rich domain, a double stranded β-helix domain and binding sites for the cofactors Fe(II) and 2oxoglutarate. At their amino-terminal region, TET1 and TET3 have a CXXC DNA-binding domain. Interestingly, during evolution, the segment encoding the CXXC domain of TET2 was separated from the region encoding the catalytic domain and is now encoded separately by a neighboring gene, IDAX (also called CXXC4).
For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.
