Does NPY Play a Role in Maintaining The Weight Setpoint?

fat ratsAs regular readers of these posts are well aware, the Holy Grail of obesity is how to lower the body weight setpoint , which tends to reset to progressively higher weights with weight gain and then acts to “defend” against weight loss, virtually guaranteeing weight regain in the vast majority of people who try to lose weight.

Now, a study by Yonwook Kim and Sheng Bi published in the American Journal of Physiology, shows that knocking down neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) can reverse the weight gain induced by a high-fat diet in rats.

Following the induction of significant weight gain by feeding rats a high-fat diet (HFD), which not only increased body weight but also induces insulin resistance, the obese rats received bilateral DMH injections of an adenovirus vector that specifically knocked down NPY in this region of the brain.

Not only did the NPY knockdown rats exhibit normal food intake and a reduced body weight, their glucose tolerance and insulin sensitivity also reverted to that seen in lean control rats, an effect that was maintained even over weeks of follow up.

While these studies do not exactly prove the importance of NPY in the establishment or maintenance of the body weight “set point”, they do suggest that blocking NPY in the DMH (e.g. through an NPY inhibitor) may provide a potential target for the treatment of obesity and diabetes.

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