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Considering the estrogen receptor, hypermethylation of the estrogen receptor 1 ( ESR1 ) promoter by mechanisms involving zinc finger E-box-binding homeobox 1 (ZEB1) and interleukin-1β (IL-1β) reduces its transcription and, therefore, ERα protein expression which confers resistance to tamoxifen treatments [149,150,151]

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This provides a potential mechanism whereby NPY/AgRP neurons can maintain a high ghrelin-induced firing rate during low energy states, whereas the anorexigenic pro-opiomelanocortin (POMC) neurons with their lack of GHSR receptor-induced UCP2 activation cannot buffer against ROS, as well, and thus, cannot maintain neuronal firing during starvation [45]