You are what you eat: discovery of a new process for how your brain controls how many calories you eat and how many calories you burn
Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling [See the original abstract on PubMed]
Authors: Ceren Ozek, Scott E. Kanoski, Zhong-Yin Zhang, Harvey J. Grill, Kendra K. Bence
Brief prepared by: David Reiner & Isaac Perron
Brief approved by: Shachee Doshi
Section Chief: David Reiner
Date posted: March 13, 2017
Brief in Brief (TL;DR)
What do we know: Your body weight is determined by the balance of how many calories you eat and how many calories you burn. Some parts of the brain control how many calories you eat and others control how many calories you burn. Activation of one protein called TrkB is well known to reduce the amount of calories eaten, but does not affect calories burned. A different protein called PTP1B is also important for maintaining normal body weight (e.g., obese people have too much PTP1B), but scientists are not sure if it affects the number of calories you eat or the number you burn.
What don’t we know: How does PTP1B control the balance of calories eaten and calories burned? Do TrkB and PTP-1B work together, and if so, what happens when they do?
What this study shows: The scientists found that TrkB activation can increase the number of calories burned, but only if the animals don't have any PTP1B. Therefore, PTP1B helps keep weight loss in check when TrkB is activated, preventing animals from losing weight too rapidly.
What we can do in the future because of this study: This study identifies a new process in the brain that affects body weight. Decreasing PTP1B in the brain may be a potential way to treat obesity by increasing the number of calories burned.
Why you should care: Roughly 1/3 of the US population is obese, increasing costs for patients and society as a whole. Currently treatments for obesity either involve surgery and are extremely expensive or do not work long term. By understanding how the brain promotes weight loss, we can begin to identify new targets for obesity treatment.
Brief for Non-Neuroscientists
Activation of the brain-specific receptor, TrkB, can decrease food intake. A different protein, protein-tyrosine phosphatase 1B (PTP1B), is increased in obesity and has some role in regulating body weight, but how it does this is unclear. This study explored whether TrkB and PTP1B interact to regulate calories consumed and calories burned. Here, the authors show that PTP1B binds and regulates TrkB, which ultimately affects body weight through changes in body temperature (i.e., calories burned). Specifically, TrkB activation reduces food intake in normal mice, but in mice lacking PTP1B, TrkB activation also increases body temperature with no effect on food intake. Thus, PTP1B reduces the effects of TrkB on weight loss by blocking body temperature increases. If we can block PTP1B in obese people, it may be a new way to accelerate weight loss in this population.
Brief for Neuroscientists
Protein-tyrosine phosphatase 1B (PTP1B) is elevated in obesity and negatively regulates leptin signaling. Therefore, it is assumed that PTP1B deficiency could stimulate negative energy balance by restoring leptin sensitivity. Here, the authors show that PTP1B also interacts with BDNF and its receptor, TrkB, to regulate energy balance. PTP1B overexpression suppresses BDNF/TrkB signaling, while PTP1B inhibition enhances BDNF/TrkB signaling. Mice administered BDNF show reductions in food intake, but no effects on core body temperature (i.e., energy expenditure). Importantly, mice lacking PTP1B have no caloric intake effects, but show increased core body temperature when administered BDNF. Therefore, BDNF-TrkB signaling is capable of reducing caloric intake on its own, but can also increase energy expenditure (and thus further weight loss) when PTP1B is absent. Thus, PTP1B could potentially be a drug target to accelerate weight loss in obese patients.