Source: Thailand Medical News Jan 27, 2020 4 years, 2 months, 4 weeks, 16 hours, 46 minutes ago
Have you ever eaten something, gotten sick and then didn’t want to
eat that food again because of how it made you feel? That’s because a signal from the gut to the
brain produced that sickness, creating a taste aversion.
Typically, conventional wisdom renders there’s one circuit in the
brain that suppresses
eating and it comes from the stomach and makes you feel sick if you activate it too hard. Eating a portioned meal makes your body happy, though, even while stimulating a signal to the
brain to stop
eating, according to Michigan Diabetes Research Center’s director, Dr Martin Myers Jr., M.D. Ph.D.
Dr Myers Told
Thailand Medical News, “Therefore, there must be a circuit that stops normal feeding without the adverse effects, right?”
A new study may have discovered this second circuit in mice. Dr Myers along with Dr Randy Seeley, Ph.D, the director of the Michigan Nutrition Obesity Research Center, and a team of medical researchers sought to better understand which part of the
brain curbs
appetite and which
neurons play a role in making mice want to
eat or not
eat.
The findings of the study was published in the journal
Cell Metabolism.
It was observed that the gut-
brain signal that suppresses appetite is triggered by a type of
neuron, containing calcitonin receptor (CALCR), which lives in a structure of the hindbrain called the medulla. Interestingly enough, these
neurons didn’t need to be active in the
brain for gut sickness to cause an aversive response.
Dr Myers, whose group found they could genetically activate those CALCR
neurons to do just that added, “This suggested we might be able to dissociate the
brainstem systems that stop feeding from those that cause nausea.”
As there are neurons that can suppress
eating but also cause aversive effects, that must mean there are different types of
neurons, or circuits, in the
brain that can terminate feeding with differing emotional responses.
Upon inactivating the CALCR
neurons, the researchers were surprised to make another discovery, which contradicted the idea that the
brain only controls short term meal sizes and consumption.
It was discovered that turning these
neurons “off” didn’t only interfere with the suppression of feeding by gut signals, but it also caused an ongoing increase in food intake. The mice became
obese, suggesting that the
brainstem systems don’t only control meal size, but the amount of food consumed long term. This created
a predisposition to
obesity because of the energy imbalance in the mice (more input than output).
Whereas, activating CALCR
neurons decreased the mice’s food intake and body weight without any aversive gut effects. In the study, Dr Myers and his team found another
neuron, CCK, also decreased food intake and body weight but created an aversive internal response, unlike the CALCR
neurons. The difference between the two
neurons was found in their circuits.
Dr Myers added, “CCK activates what we would call a ‘yucky circuit’. The
neurons activate a certain cell, CGRP cells, which create that sick feeling. Unlike CCK, activated CALCR
neurons follow a ‘yummy circuit,’ activating non-CGRP cells.”
Currently,
obesity affects more than one-third of the adult population in developed countries, which can lead to diabetes or other serious, long-term health conditions like heart disease, explains Dr Myers, who is also the director of MDiabetes.
Though many
diet drugs work, they often make people feel nauseous after they take them.
Obesity remains a condition difficult to pharmaceutically manage, since the treatment options have limited therapeutic utility. A
drug that turns “on” CALCR and turns off “CGRP” could greatly benefit patients with
obesity by suppressing feeding and creating a long term control of food intake and body weight.
Dr Myers further added, “If we could figure out a
drug for individuals with
obesity that suppresses food intake to produce long term weight loss without the negative side effects, it could absolutely change someone’s life.”
Reference: “Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding” by Wenwen Cheng, Ian Gonzalez, Warren Pan, Anthony H. Tsang, Jessica Adams, Ermelinda Ndoka, Desiree Gordian, Basma Khoury, Karen Roelofs, Simon S. Evers, Andrew MacKinnon, Shuangcheng Wu, Henriette Frikke-Schmidt, Jonathan N. Flak, James L. Trevaskis, Christopher J. Rhodes, So-ichiro Fukada, Randy J. Seeley, Darleen A. Sandoval, David P.Olson, Clemence Blouet and Martin G. Myers Jr., 16 January 2020, Cell Metabolism.
DOI: 10.1016/j.cmet.2019.12.012
