PPARGC1A and obesity due to melanocortin 4 receptor deficiency: However, most past studies have failed to unravel the underlying mechanisms (Yang et al., 2011; Kabir et al., 2014; Martinez et al., 2016) with the exception of one study, in which RAP1 protected mice from obesity by promoting the transcription of Pparα and Pgc1α by directly binding to the upstream regulatory regions of these genes (Martinez et al., 2010, 2013).