9.B.228. The TMEM18 (TMEM18) Family
An intergenic region of human chromosome 2 (2p25.3) harbors genetic variants which are among those most strongly and reproducibly associated with obesity. The gene closest to these variants is TMEM18. Tmem18 expression in the murine hypothalamic paraventricular nucleus (PVN) was altered by changes in the nutritional state (Larder et al. 2017). Germline loss of Tmem18 in mice resulted in increased body weight, which was exacerbated by a high fat diet and driven by increased food intake. Selective overexpression of Tmem18 in the PVN of wild-type mice reduced food intake and also increased energy expenditure. Larder et al. 2017 provided evidence that TMEM18 has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex. Their data support the hypothesis that TMEM18 itself, acting within the central nervous system, is a plausible mediator of the impact of adjacent genetic variation on human adiposity.