产品描述:
Fat mass and obesity-associated (FTO) protein is a nuclear-residing N6-methyladenosine (m6A) RNA demethylase that is encoded by the FTO gene in humans.{48528,19167,48529} It is composed of an N-terminal domain similar in structure to members of the AlkB non-heme iron-containing dioxygenase family and a C-terminal domain that is not similar to other known domains.{35510} The N-terminal domain contains a loop not found in other AlkB proteins that may be responsible for its specificity for single-stranded nucleic acids. FTO is highly expressed during development and in the adult brain, adipose tissue, and muscle and its expression is modified by the availability of essential amino acids in vitro and following fasting or a chronic high-fat diet in vivo in mice.{48529,48530,48531} FTO regulates mRNA splicing and is required for adipogenesis.{48528,48532} Knockdown of Fto in mice increases m6A-containing transcripts of the adipogenesis-related gene Runx1t1, enhances binding of the splicing regulatory protein Srsf2 to Runx1t1, which induces the inclusion of Runx1t1 exon 6 and the production of long Rnx1t1 transcripts, and leads to inhibition of pre-adipocyte differentiation. Fto is associated with obesity in transgenic mouse models, with overexpression increasing food intake and weight gain and knockout reducing body weight, body length, fat mass, and white adipose tissue, as well as increasing energy expenditure while decreasing locomotor activity.{19167} FTO SNPs are associated with body mass index and obesity risk in humans.{48531,48533}