In fact, ER stress plays a role in the development of obesity and leptin resistance (Zhang et al., 2008; Lionetti et al., 2009; Ozcan et al., 2009; Mollica et al., 2011) and genetic loss of Mfn2 generates ER stress (Sebastián et al., 2012). Here, MFN2 is linked to obesity due to melanocortin 4 receptor deficiency.