In conclusion, PTEN insufficiency leads to fatty liver (whether by liver specific knockout, where systemic insulin sensitivity is maintained as fat preferentially accumulates in liver; or by obesity per se, where excess FFA released by overloaded adipocytes of SAT can downregulate PTEN in liver via FFA; this of course, will be associated with insulin resistance). Here, PTEN is linked to obesity due to melanocortin 4 receptor deficiency.