by Biologists have shown it's possible to reduce the weight of mice by activating brown fat to convert energy into heat on demand
In the battle between people and their body mass, there is a newly discovered biological effect that may help people with ‘the right kind’ of fat lose weight by increasing the levels of a readily available molecule in their body.
It relies on the previously unknown relationship between the molecule succinate (C4H4O4-2 for chemistry fans), and ‘thermogenic adipocytes’, commonly known as brown fat. The classic white fat cell contains a single drop of fat, while brown fat, which can be found either separately or mixed with white fat in ‘beige’ areas, contains fat also, but in a greater quantity of smaller drops, and also has large amounts of mitochondria (which are rich in iron, and therefore give the cells a red-brown colour)
Mitochondria turn fuel sources, like glucose or fat, into energy; in the case of brown fat, they allow for the cell to burn fat and other energy sources to make heat. It has been known for some time that the easiest way to activate brown fats is to expose the body to cold temperatures. The thermal energy produced by brown fat is the major way that the body regulates its temperature in the cold, alongside making the muscles shiver.
However a new study published in Nature, undertaken by a team led by Edward Chouchani, assistant professor of cell biology at Harvard Medical School and of cancer biology at the Daner-Farber Cancer Institute, has found that succinate offers an alternative method. “It's really quite a remarkably simple and tractable way to switch on the therapeutic activity of these cells,” Chouchani explained.
Succinate is produced within mitochondria (such as those found in brown fat) during and is an intermediate product of the tricarboxylic acid cycle (also known as the TCA, citric acid, or Krebs cycle), the reaction that produces chemical energy for cells. It is also produced on an industrial scale to make polymers for use in cars and electronics, and as a flavouring or acidity regulator for food. “One of the interesting things about this molecule is how simple it is,” Chouchani says. “It's very small, you can order it off the shelf for not that much money, it's super cheap.”
What Chouchani and his team discovered, after analysing in mice which metabolites (the various chemicals that appear in the TCA cycle) that are present in brown fat cells during thermogenesis, was that the cells have an abundance of succinate present within them, especially in cold temperatures, and that they also have the remarkable ability to gather additional succinate molecules from the bloodstream.
The cells can then metabolise and create reactive oxygen species (ROS) using the succinate, which is odd in itself, as these ‘free radicals’ are normally thought of as causes or evidence of cell damage, but are in fact key in making this reaction happen. It was the previous discovery of the surprising presence of the ROS molecules during the thermogenic reaction that set Chouchani and his collaborators on the path to this new discovery.
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In the battle between people and their body mass, there is a newly discovered biological effect that may help people with ‘the right kind’ of fat lose weight by increasing the levels of a readily available molecule in their body.
It relies on the previously unknown relationship between the molecule succinate (C4H4O4-2 for chemistry fans), and ‘thermogenic adipocytes’, commonly known as brown fat. The classic white fat cell contains a single drop of fat, while brown fat, which can be found either separately or mixed with white fat in ‘beige’ areas, contains fat also, but in a greater quantity of smaller drops, and also has large amounts of mitochondria (which are rich in iron, and therefore give the cells a red-brown colour)
Mitochondria turn fuel sources, like glucose or fat, into energy; in the case of brown fat, they allow for the cell to burn fat and other energy sources to make heat. It has been known for some time that the easiest way to activate brown fats is to expose the body to cold temperatures. The thermal energy produced by brown fat is the major way that the body regulates its temperature in the cold, alongside making the muscles shiver.
However a new study published in Nature, undertaken by a team led by Edward Chouchani, assistant professor of cell biology at Harvard Medical School and of cancer biology at the Daner-Farber Cancer Institute, has found that succinate offers an alternative method. “It's really quite a remarkably simple and tractable way to switch on the therapeutic activity of these cells,” Chouchani explained.
Succinate is produced within mitochondria (such as those found in brown fat) during and is an intermediate product of the tricarboxylic acid cycle (also known as the TCA, citric acid, or Krebs cycle), the reaction that produces chemical energy for cells. It is also produced on an industrial scale to make polymers for use in cars and electronics, and as a flavouring or acidity regulator for food. “One of the interesting things about this molecule is how simple it is,” Chouchani says. “It's very small, you can order it off the shelf for not that much money, it's super cheap.”
What Chouchani and his team discovered, after analysing in mice which metabolites (the various chemicals that appear in the TCA cycle) that are present in brown fat cells during thermogenesis, was that the cells have an abundance of succinate present within them, especially in cold temperatures, and that they also have the remarkable ability to gather additional succinate molecules from the bloodstream.
The cells can then metabolise and create reactive oxygen species (ROS) using the succinate, which is odd in itself, as these ‘free radicals’ are normally thought of as causes or evidence of cell damage, but are in fact key in making this reaction happen. It was the previous discovery of the surprising presence of the ROS molecules during the thermogenic reaction that set Chouchani and his collaborators on the path to this new discovery.
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