but the cause is different. If you get nothing else from this chapter, remember the next sentence: different causes can yield the same result. Because the fix ends up being the same.The DIO ratTo complete the picture I ve been drawing you of potential problems in the leptin system, I need to switch from mouse to rat and talk about one more animal model, the DIO rat. DIO stands for dietary induced obesity, and refers to an otherwise normal rat who gets fattened up on a diet of high calorie, tasty, high fat food (basically cookie dough) and no exercise; which is a lot like our modern American lifestyle. Over time, this otherwise normal rat gets fatter and fatter, raising leptin levels higher and higher. As leptin goes up and up, eventually its little rat brain becomes leptin resistant. It may be a transporter defect, or a hypothalamic receptor defect, or both. The exact reason why doesn really matter. In response to constant pounding by high levels of leptin, the receptors stop working as well and a lower leptin signal gets sent. As above, this is identical to what happens in insulin resistance, on top of whatever genetic effects are present, chronically high levels of insulin cause the receptor to become resistant over time. Over time, the DIO rat will start to defend its bodyweight/bodyfat level at higher and higher levels (setpiont goes up) as the brain itself adapts. It looks like there may be permanent neural changes occurring which may be why setpoint can t be brought back down. Finally, we have a model that sounds like what happens in humans: couple a poor diet with little exercise, and you get increasing bodyfat and leptin resistance. The difference being that some humans (which researchers call obesity prone) are probably starting off a little leptin resistant to begin with. Their lifestyle just makes it worse. But just because it sounds similar, does that mean that it works the same way in humans That appears to be the case. While absolute leptin resistance in humans is very rare, cases of partial leptin resistance in humans have been documented and seem to occur in members of the same family, along with obesity (20,21). This suggest that obesity/fat gain and leptin resistance go hand in hand, which is no real shock. It also means that leptin resistance has a genetic component
