LEP and obesity due to melanocortin 4 receptor deficiency: As leptin receptor desensitization typical of HFD obese mice occurs mostly, if not uniquely, in the hypothalamic regions of HFD mice, whereas excessive OxA levels were found here in both models of obesity investigated, we surmise that the observed decrease in NR2B expression is due primarily to lack of leptin signaling as proposed previously by other authors61, with potential consequences also on 2-AG levels and CB1 activation.