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Brain cells that aid appetite control identified

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It’s rare for scientists to get what they describe as “clean” results without spending a lot of time repeating the same experiment over and over again. But when researchers saw the mice they were working with doubling their weight within a month or two, they knew they were on to something.

“About twenty years ago there was a big step forward in our understanding of obesity when researchers discovered that our appetite is controlled by a key molecule called leptin.”

“Leptin is a hormone which is produced by our fat cells, and is delivered by the blood to the brain to signal the brain that we are full and can stop eating,” explains Dr. Maia Kokoeva who is affiliated both with McGill University and the Research Institute of the McGill University Health Centre.

“But even though receptors for leptin were discovered soon after in the hypothalamus, a brain area that regulates food intake and body weight, it has remained unclear how exactly leptin is detected.”

So about four years ago, Kokoeva and her team set out to explore which brain cells might play a role in the process of leptin sensing and weight gain. The answer, it turns out, lies in the median eminence.

The median eminence is a brain structure at the base of the hypothalamus. It is a bit like a busy hub or market place through which hormones and molecules of various kinds travel in both directions between the brain and the bloodstream to ensure that the body functions smoothly.

The McGill research team has now discovered that without a particular group of cells (known as NG2-glia cells) in place in the median eminence, the leptin receptors in the brain never receive the messages from the body telling it that it is sated.

“Most of the brain is a well-protected fortress, designed to shelter delicate nerve cells,” says Kokoeva.

“The median eminence is outside these protections, and so can be a dangerous environment for the nerve cells that detect leptin. We think that the NG2-glia cells act to support and shelter the leptin receptor neurons, enabling them to instruct the body when to stop eating.”

“We developed an interest in NG2-glia cells in this specific part of the brain because unlike neurons, during much of our adult lives these cells are constantly dividing and they do so most actively in the median eminence,” says Tina Djogo, one of two lead authors on the study.

“But though these cells were first described about thirty years ago it has been difficult so far to pinpoint their exact functions in the adult brain.”

Because of their particularly high turnover in the median eminence, the researchers wondered if the NG2-glia cells might play a role in leptin sensing and therefore in appetite control. So they used a drug to kill the NG2-glia cells in the median eminence of a group of mice and then watched to see whether there was a difference in food intake. The results were stunning.

Within three days after they started to receive the medication, some of the mice dubbed “gainers” had already started to eat more compared with the control group of mice who had not received medication. And by 30 days afterwards, the weight of some of the mice had doubled – from 25 grams to around 50 grams.

“But what was most exciting to us, was that even though NG2-glia are found across the brain” explains Sarah Robins, a lead author on this study, “it was only when we removed these cells from the median eminence that we saw this clear increase in body weight.”

The researchers then corroborated the role of the NG2-glia cells in the median eminence in appetite control through experiments using genetically modified mice, and also by using irradiation. This latter discovery suggested an explanation for a previously unexplained phenomenon in human brain cancer survivors.

“People who have been treated for brain tumours using radiation to block cell proliferation often become overweight,” says Kokoeva.

“However, there has never been any satisfactory explanation, but our experiments in mice now suggests that the reason for this weight gain may be the loss of NG2-glia in the median eminence as a result of radiation.”

The researchers are hopeful that the identification of NG2-glia in the median eminence as crucial elements in body weight and appetite control will pave the way to new targeted anti-obesity approaches directed towards maintaining or raising the NG2-glia population in the median eminence.

Djogo, T., Robins, S., Schneider, S., Kryzskaya, D., Liu, X., Mingay, A., Gillon, C., Kim, J., Storch, K., Boehm, U., Bourque, C., Stroh, T., Dimou, L., & Kokoeva, M. (2016). Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control Cell Metabolism, 23 (5), 797-810 DOI: 10.1016/j.cmet.2016.04.013

5 responses

  1. Tiffany

    Leptin is an important hormone in appetite, but it’s not the only factor. What about ghrelin that is secreted when the stomach is empty? Since its receptors are on the same cells as receptors for leptin, would an increase in NG2-glia also affect ghrelin? And even if there is a way to increase the number of NG2-glia, that doesn’t necessarily mean that it would be effective in weight loss because people eat regardless of whether or not they’re hungry.


    May 22, 2016 at 5:58 pm

    • Holly

      You make a valid point with the grehlin.. That should definitely be addressed in further research and progress. You would think if their was a problem with the the NG2-glia cells then that may be an indication that there is something wrong with the grehlin as well, or even put the secretion to a hault! But if some diseases or disorders are causing lack of NG-2 glia then there is a possibility that grehlin is working at an over exasperated rate. Therefore, if there is a way to increase the NG2-glia, then maybe it will result in regular appetite, meaning grehlin secretion would then start functioning at a normal rate? Just a thought!


      June 8, 2016 at 2:00 pm

  2. Hailey Chesser

    Leptin research has completed monopolized the way we look at how hunger is regulated in the body. While I agree with Tiffany, that there are many other forces of both physiological and environmental decent, it is difficult to argue with all of the results we have seen, especially in the trials we have done with rats and mice. The discovery of the NG2-glia cells acting to support and shelter the leptin receptor neurons, enabling them to instruct the body when to stop eating, is a discovery that cannot be ignored and gives us more insight as to how leptin’s role in regulating appetite presents itself. If NG2-glia cells play a role in leptin sensing and therefore in appetite control, we could alter the expression of this hormone by means other than hormone treatment, which we have done in the past with rodent studies. It really would pave the way to new targeted anti-obesity approaches directed towards maintaining or raising the NG2-glia population and therefore maintaining or controlling appetite.


    June 3, 2016 at 6:15 am

  3. Elizabeth Hall

    I think this research is interesting and could significantly help the medical field. It would be interesting to do research on the amount of NG2-glia individuals have. Does more or less NG2-glia make individuals more likely to gain weight compared to others? Also I think if there is a way to shut off NG2-glia there is a possibility to add more NG2-glia to an individual? For example, adding NG2-glia to individuals with diabetes or thyroid issues that causes them to gain a significant amount of weight may allow for them to lose weight. I think all of these questions are good angles to look at this research. It is good research for the cancer community as well.


    June 7, 2016 at 6:20 pm

    • Holly

      I think part of the point in sharing this research was to enlighten individuals on why some people experience the feeling of “never being full” and continue to eat and gain weight, and/or why some issues like thyroid problems, diabetes, and radiation in the brain merely cause weight gain. It seems as if these diseases/disorders potentially cause lack of these special cells which throw off the communication system from the brain and the blood stream. The absence of the NG2-glia cells in the median eminence disrupts the communication between those cells and the protein leptin receptors (special hormone). Without the leptin receptors retrieving the message from the NG2-glia cells, it does not allow the body to store fat as it regularly should. If the NG2-glia can be restored however, then it seems as if normal appetite will replenish and no weight gain will occur in these diseases/disorders. That is the way I understood the article, I hope that helped some of your questions! If I am wrong then someone else can comment below so I gain some knowledge on a different perspective. Thank you.


      June 8, 2016 at 1:57 pm

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