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New research suggests better anti-obesity drugs



  New research suggests better drugs for obesity
Neurons in the brain stem are activated in response to heat. By inhibiting these cells in mice, the researchers were able to make the animals eat less and burn more calories. Credit: Molecular Genetics Laboratory at Rockefeller University

Effective weight loss strategies require less eating, more calories burned ̵

1; or ideally both. But for the more than 90 million Americans who suffer from obesity, a disease that contributes to diseases ranging from cancer to heart disease, changing behavior is difficult or ineffective – which is why scientists have long searched for drugs that help people to cure pounds. Effective and long-lasting treatments have so far eluded them.

In a new report published in Cell researchers in the laboratory of Jeffrey M. Friedman propose a new route in the search for drugs for obesity. Working with a Princeton University team, they discovered that a group of brain cells previously shown to regulate hunger also controlled energy consumption. And since our body weight depends both on the calories we consume and the energy we consume, these results could lead to a new type of weight loss medication acting on both sides of the energy equation.

Pure Energy, Energy Out [19659006] So far, most studies on obesity have focused on the biological mechanisms that determine how much we eat. The manipulation of the neural circuits controlling our calorie intake, however, has not led to largely successful anti-obesity drugs. Marc Schneeberger Pané, a postdoctoral researcher at Kavli NSI in Friedman's lab, therefore started a project to study the processes of burning energy instead.

Mammals such as mice and humans consume energy in a variety of ways, and the generation of heat is one of the most important. When the ambient temperature drops, we burn more fuel to maintain a consistent body temperature. If it rises, we burn less. We even have a special form of fatty tissue, the so-called brown fat, which is burned to produce heat directly.

Scientists knew that some populations of temperature-sensitive neurons in the hypothalamic region of the brain play a role in regulating heat production and thus energy consumption. However, they did not know exactly how these neurons exerted their influence or whether other cells outside the hypothalamus played a similar role.

Double task

Schneeberger Pané and his colleagues, including doctoral student Luca Parolari, began mapping the brain regions activated by an increase in ambient temperature. They used an advanced 3-D imaging technique called iDISCO developed by Rockefeller to examine the brain of mice exposed to hot temperatures for signs of neuronal activity.

As expected, the team recognized activity in the hypothalamus. However, they also observed the activity of a particular group of neurons in a part of the brainstem known as the dorsal raphe nucleus – and, to the researchers' surprise, these were the same neurons that were used in the laboratory two years ago as critical for controlling the brain Hunger.

"Our new findings show that these neurons regulate the energy balance by regulating both food intake and energy consumption through partially overlapping switching mechanisms," says Alexander R. Nectow, who led the Princeton University team.

The possibility that these cells, previously referred to as "hunger neurons" by the lab, could regulate both hunger and energy use, suggesting that they could serve as powerful levers for controlling body weight.

"We were very excited," remembers Schneeberger Pané, adding that he and his colleagues consider these multitalented neurons a "new horizon in obesity research."

The researchers used sophisticated biochemical techniques to turn these temperature-sensitive brain stem neurons on and off in turn. They discovered that activation of the neurons lowered the temperature of the animal's brown fat, which is burned to produce heat, as well as body temperature. Meanwhile, suppression of neurons has increased heat production – and, as scientists have shown earlier, has also reduced animal hunger.

Eat less, burn more

But to burn heat by burning brown fat is not the right way. Only in this way can you consume energy. Physical activity burns calories as well as all the basic tasks that keep the body alive: breathing, digesting food and so on. Therefore, the researchers place the mice in special cages equipped with sensors to track their movements and measure how much carbon dioxide they produce and how much food, water and oxygen they consume. The aim was to find out if the temperature-sensitive hunger neurons of the dorsal raphe core can control energy consumption not only by regulating the temperature, but also in other ways.

Again, the results were clear: just as activation of the neurons caused heat generation. The fall also caused movement, metabolic activity and overall energy expenditure. However, the suppression of the neurons made them all rise.

The team has already begun to search for unique receptors in these multi-purpose neurons that control both hunger and energy consumption. The idea is to identify targets that can be used to develop novel anti-obesity drugs that can trigger a double stroke.

"If you inhibit these neurons, they suppress food intake and increase energy consumption." says Schneeberger Pané. Finding out how to silence them in humans could allow for a double-effective attack on a massive public health problem.


Famine-controlling brain cells could pave the way for new anti-obesity drugs


Further information:
Marc Schneeberger et al., Regulation of Energy Consumption by Brainstem GABA Neurons, Cell (2019). DOI: 10.1016 / j.cell.2019.05.048

Information in Journal:
Cell




Contributed by
Rockefeller University




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New research suggests better anti-obesity drugs (2019, 27 June)
retrieved on June 28, 2019
from https://medicalxpress.com/news/2019-06-prospect-anti-obesity-drugs.html

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