These data suggest that the chromosome 6p12 signal exerts its predominant effect on fat accumulation at multiple sites, a finding consistent with the known biology of TFAP2B, which is the most obvious candidate gene in the locus. TFAP2B encodes a transcription factor preferentially expressed in adipose tissue, and over-expression of the transcript in 3T3L1-adipocytes leads to insulin sensitivity via enhanced glucose transport and increased lipid accumulation [21],[22]. Over-expression of TFAP2B also down-regulates expression of the insulin-sensitizing hormone adiponectin by direct transcriptional repression [23]. Genetic variants within TFAP2B have recently been reported to correlate positively with TFAP2B transcript levels in adipose tissue [24]. Thus, TFAP2B can be added to the growing list of loci influencing overall adiposity [10],[14],[16],[17]. However, in contrast to most of the variants previously implicated in monogenic or multifactorial forms of obesity, which exert their effects on overall adiposity at the hypothalamic level [10], [12]–[14], [16]–[17], TFAP2B may be involved in global adipocyte response to positive energy balance.
