Scientists from the Weizmann Institute have added another element to the puzzle of obesity. They demonstrated how and why a specific protein, which is active in a small part of the brain, contributes to the increase of body weight. Publication regarding to this topic appeared in the Cell Metabolism journal.


Obesity is linked not only with excessive accumulation of fat tissue, but with adverse effects on health. The placement of fatty tissue is also significant. Abdominal obesity is especially pathological. Excess of body weight increases the risk of cardiovascular diseases, diabetes mellitus type 2, obstructive sleep apnea syndrome, gallstones, renal diseases, some types of cancer (e.g. endometrial cancer), inflammation of bones and joints, therefore reducing the expected length of life. Severe obesity leads to disability. The most common cause of obesity is eating too big amounts of food. In addition, in the pathogenesis of overweight other factors are implemented – genetic, biological, pharmacological, environmental and psychological. Genetic factors play a role not only in promoting obesity, but increasing susceptibility to its development. Syndromes associated with the excessive weight of the body are rare (Prader-Willi, Bardet-Biedl, Cohen) and they do not explain the mechanism of obesity formation. It is considered that in most human gaining of the body weight is determined polygenic. Mutations may concern genes responsible for collection of food, metabolism and adipocytes development. Obesity occurs two times more frequent in identical twins, than in not-twin siblings. Moreover, the weight of the adults brought up in substitute families is compatible with the mass of the biological parents.

Professor Ari Elson with his team made their discovery working on genetically engineered female mice. These animals showed lack of protein – tyrosine phosphatase epsilon (PTPe). Initially, the aim of research was the analysis of the prevalence of osteoporosis among mice, so their ovaries were removed. After removal of the ovaries, the typical reaction is assuming the body weight, so the researchers were surprised that the observed animals preserved its mass. The next step was to use high-fat diet in mice, which, despite an increase in the amount of food did not gain weight. In addition, they used more calories and had more stable blood glucose levels.

To explain this phenomenon, researchers have turned their attention to the hypothalamus, a region of the brain involved in hormonal and nervous signaling. Hypothalamus plays an important role in regulating body weight, through inter alia, the control of appetite and physical activity. Professor Elson and his team discovered that PTPe blocks the signals transmitted by leptin – hormone responsible for body weight. PTPe is responsible for the interaction of leptin with a receptor in hypothalamus, inhibiting certain proteins and turning down the signal. Leptin reduces appetite and increases physical activity. Paradoxically, obese people often have an excess of this hormone in the blood. This is because their organism produces leptin, but the cells become resistant to its effects, causing intensification of hormone production. The study shows that PTPe plays a role in the resistance to leptin. Mice with lack of PTPe were exceptionally susceptible to leptin, what more this phenomenon wasn’t altered by ageing, the removal of the ovaries or high-fat diet. This discovery suggests that inhibiting PTPe in human could make the cells “sensitive” to leptin and allow to lose body weight. However, this requires further research. There will be a lot of volunteers…

Written by: Karolina Kłoda MD, PhD

Source:
1. Liat Rousso-Noori, Hilla Knobler, Einat Levy-Apter, Yael Kuperman, Adi Neufeld-Cohen, Yonat Keshet, Vasudheva R. Akepati, Richard A. Klinghoffer, Alon Chen, Ari Elson. Protein Tyrosine Phosphatase Epsilon Affects Body Weight by Downregulating Leptin Signaling in a Phosphorylation-Dependent Manner. Cell Metabolism, 2011; 13 (5): 562-572 DOI: 10.1016/j.cmet.2011.02.017
2. http://www.sciencedaily.com­ /releases/2011/05/110504091840.htm
3. http://en.wikipedia.org/wiki/Obesity