Furthermore, a study by Ozcan and colleagues revealed an obesity-dependent increase in endoplasmic reticulum (ER) stress within hypothalamic neurons, and found that tunicamycin-induced ER stress in the brains of lean mice was sufficient to block hypothalamic STAT3 phosphorylation, following IP leptin administration (Ozcan et al. 2009). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.