Rat models in obesity research : functions for PMCH and LPIN1 in energy homeostasis regulation

The number of people that are overweight or obese has shown an alarming increase worldwide in past three decades. Good news however is that, at least in the US , this increase seems to have stalled. As mentioned in chapter 1, the obese population can be roughly divided into two groups. The first group is the small fraction (~5-10%) of people with obesity caused by (mono)-genetic mutations, endocrine disorders, or medication. This fraction has remained relatively stable over time. The second group is the large fraction of people with obesity that is caused by a combination of high-caloric food intake, decreased physical activity, and genetic susceptibility. As the general knowledge regarding energy homeostasis has increased significantly, the development of an anti-obesity treatment based on a key neuropeptide or receptor involved in energy regulation might be not far away. However, the increased general knowledge has also demonstrated the complexity and integration of different brain systems, all driving one goal: the correct regulation of body weight and subsequent health. Affecting the function of one such brain system through pharmaceutical intervention might thus result in adaptations and subsequent compensation in other brain regions. This will inevitably obstruct or even impair the development and function of a potential anti-obesity treatment. The chance that such a potential anti-obesity treatment is based on the MCH - MCH 1R-system is small, but still present. If Lipin 1 function can be at the basis of a treatment for lipodystrophy, paralysis, or both, has to be investigated in the future. It is conceivable that an effective pharmaceutical anti-obesity treatment with a one-size fits-all characteristic might never be developed. Therefore I advice everybody to first shift their trust from the scientists to themselves: eat healthy and exercise regularly!