A hormone called amylin can tell us to stop overeating (even if we really, really love cookies and swear we only want one more)

or technically,

Amylin acts in the lateral dorsal tegmental nucleus to regulate energy balance Through GABA Signaling.

[See Original Abstract on Pubmed]

Authors of the study: David J. Reiner, Elizabeth G. Mietlicki-Baase, Diana R. Olivos, Lauren E. McGrath, Derek J. Zimmer, Kieran Koch-Laskowski, Joanna Krawczyk, Christopher A. Turner, Emily E. Noble, Joel D. Hahn, Heath D. Schmidt, Scott E. Kanoski, Matthew R. Hayes

Have you ever had one too many chocolate chip cookies? Maybe you’ve eaten so much that you felt sick? Sometimes we eat when we’re not hungry. This is because, in addition to filling us up, delicious food activates the parts of our brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. that make us feel pleasure (also known as the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.’s “reward areas”). Dave Reiner, a neuroscience graduate student in Matt Hayes’s lab, wondered if some people feel the rewarding effects of food more strongly than others. To figure this out, he asked whether one of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.’s specialized reward areas can sense a hormone called amylin, which gets released when you’re full. Dave thought that if the reward areas could sense amylin, then they might be able to tell you to stop eating, no matter how delicious your grandma’s cookies are....

Here’s how this could work: after a meal, your pancreas produces a hormone called amylin that travels through your bloodstream into your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Once it’s in your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., amylin binds to proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. called “amylin receptorsA protein on a cell’s surface that binds to specific molecules (i.e. other proteins or chemicals). Typically, a receptor is said to fit with its partner molecule(s) like a lock and key. When bound by the right molecule, receptors often transmit signals to the rest of the cell..” BrainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. areas that contain these receptorsA protein on a cell’s surface that binds to specific molecules (i.e. other proteins or chemicals). Typically, a receptor is said to fit with its partner molecule(s) like a lock and key. When bound by the right molecule, receptors often transmit signals to the rest of the cell. can sense amylin, which tells them that you are full. Dave found that there are amylin receptorsA protein on a cell’s surface that binds to specific molecules (i.e. other proteins or chemicals). Typically, a receptor is said to fit with its partner molecule(s) like a lock and key. When bound by the right molecule, receptors often transmit signals to the rest of the cell. in a reward area called the lateral dorsal tegmental nucleus (LDTg). This made Dave wonder what amylin might be doing in the LDTg. He was especially curious because the LDTg is best known as a reward area, not as a part of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. that controls hunger or metabolism. To test this, Dave used a drug to turn on the amylin receptorsA protein on a cell’s surface that binds to specific molecules (i.e. other proteins or chemicals). Typically, a receptor is said to fit with its partner molecule(s) like a lock and key. When bound by the right molecule, receptors often transmit signals to the rest of the cell. specifically in the LDTg of rats. And what he saw was really exciting: rats that received the drug ate less food and lost weight (when compared with rats that received a placebo).

This finding leads to another interesting question -- how does amylin in the LDTg limit food intake and cause weight loss? Dave didn’t do any experiments to figure this out, but he did have an idea of how it might work: because the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. cells inside the LDTg are inhibitory (this means they send “stop” signals to other brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. cells), Dave hypothesized that these “stop” signals are what caused the rats (and could cause you) to eat less. These findings could be really important for many Americans (over a third of the total US population) who struggle with obesity. If we can understand how hormones act in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. to make us feel hungry or full, we can potentially create new treatments for healthy weight management.

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

or, technically, 
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.