Israeli scientists say they’ve paved the way to turn off brain’s ‘hunger switch’

New Israeli research may pave the way for drugs that “turn off the hunger switch” in the human brain with minimal side effects, scientists say.

A receptor in the brain, melanocortin 4 (MC4), is known to control the urge to eat. It has been dubbed the “hunger switch.”

A genetically inherited malfunction with this receptor is believed to be the most common cause of obesity that is triggered by a single gene mutation, impacting an estimated 5 percent of early-onset childhood obesity.

Now, researchers at the Weizmann Institute of Science have conducted research that they say could bring about easy manipulation of the receptor among people with such a mutation.

They say it could even be used to help people who don’t have a genetic condition that directly impacts the MC4 in their efforts to lose weight, by treating the receptor as an “override” switch. When “turned off,” they say, it could suppress regular hunger.

Their research involved building a detailed 3D model of the receptor, giving unprecedented insight into how it functions, in a peer-reviewed study that was published on Thursday in the journal Science.

“It’s a switch activated by a hormone that our body secretes, which can be turned on and off,” said Dr. Moran Shalev-Benami of Weizmann Institute. “We’ve shown exactly what it looks like and outlined all of its molecular details.”

Illustrative: on-off switches (iStock by Getty Images)

Pharmaceutical companies have been racing to make drugs that manipulate MC4, but as they are doing so with limited knowledge of how the receptor works, drugs appear to bind with several receptors and affect other aspects of the brain and body, causing side effects.

The first drug of its type, setmelanotide — sold under the brand name Imcivree — was approved by the US Food and Drug Administration in November for chronic weight management, but reported side effects included spontaneous penile erections in males and adverse sexual reactions in females, as well as depression and suicidal ideation. There were also cases of nausea, diarrhea, and abdominal pain.

“Now that we know the precise molecular details of the switch, we can use this to target it very precisely and design drugs that can avoid some of the side effects that have been encountered with this first drug,” said Shalev-Benami.

Her lab at Weizmann’s Chemical and Structural Biology Department conducted the study, which involved observing the impact of setmelanotide in detail, with scientists from the Hebrew University of Jerusalem and the Queen Mary University of London.

Prof. Moran Shalev-Benami of Weizmann Institute (courtesy of the Weizmann Institute)

The study started after Hadar Israeli, a Hebrew University medical student pursuing PhD studies into the mechanisms of obesity, heard about a family in which at least eight members, who all felt constantly hungry, were severely obese. Most of them had a body mass index of over 70, which is about triple the norm.

Israeli was struck by the fact that the family’s plight was due to a single mutation that ran in the family — one affecting the MC4 receptor — and asked whether new advances in imaging biological specimens could give insights into how the receptor works.

Her supervisors contacted Shalev-Benami, who decided to launch a study into the structure of MC4, inviting Israeli to join her lab as a visiting scientist. They isolated large quantities of pure MC4 receptors from cell membranes and determined its 3D structure using cryogenic electron microscopy, an imaging technique performed at very low temperatures.

Shalev-Benami said that the first priority is to help people with genetic conditions directly affecting  MC4 but said that advances could well help others trying to diet. She commented: “If we can get rid of side effects and manipulate this receptor without interfering with other receptors and causing side effects this could help the general population of people struggling with weight loss.”

I’m proud to work at The Times of Israel

I’ll tell you the truth: Life here in Israel isn’t always easy. But it’s full of beauty and meaning.

I’m proud to work at The Times of Israel alongside colleagues who pour their hearts into their work day in, day out, to capture the complexity of this extraordinary place.

I believe our reporting sets an important tone of honesty and decency that’s essential to understand what’s really happening in Israel. It takes a lot of time, commitment and hard work from our team to get this right.

Your support, through membership in The Times of Israel Community, enables us to continue our work. Would you join our Community today?

Thank you,

Sarah Tuttle Singer, New Media Editor

Join the Times of Israel Community

Join Our Community

Already a member? Sign in to stop seeing this

You’re serious. We appreciate that!

That’s why we come to work every day – to provide discerning readers like you with must-read coverage of Israel and the Jewish world.

So now we have a request. Unlike other news outlets, we haven’t put up a paywall. But as the journalism we do is costly, we invite readers for whom The Times of Israel has become important to help support our work by joining The Times of Israel Community.

For as little as $6 a month you can help support our quality journalism while enjoying The Times of Israel AD-FREE, as well as accessing exclusive content available only to Times of Israel Community members.

Join Our Community

Join Our Community

Already a member? Sign in to stop seeing this

Source link

What do you think?

Written by Aakash Malu


Leave a Reply

Your email address will not be published. Required fields are marked *





9 Israeli-Founded Companies Reach Unicorn Status In 1st Quarter Of 2021

Geely to sell its Zeeker electric cars directly to customers · TechNode