In 2005, Oh hypothesised this may be due to impaired BBB transport mediated by unsaturated fatty acids with obesity, however a recent study by Harrison and colleagues using tissue clearing and light-sheet microscopy of fluorescently tagged leptin provides evidence that chronic HFD does not reduce leptin accumulation within the hypothalamus, compared with ND controls (Harrison et al. 2019; Oh-I et al. 2005). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.