Medical

Protein that "hacks" energy pipeline offers target for fat-burning drugs

Protein that "hacks" energy pi...
Scientists have identified a new metabolic process that they believe could be targeted for more effective fat-burning in humans
Scientists have identified a new metabolic process that they believe could be targeted for more effective fat-burning in humans
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Scientists have identified a new metabolic process that they believe could be targeted for more effective fat-burning in humans
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Scientists have identified a new metabolic process that they believe could be targeted for more effective fat-burning in humans
High-resolution imaging shows the Them1 protein at work in brown adipose tissue, organizing into structures that block energy burning
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High-resolution imaging shows the Them1 protein at work in brown adipose tissue, organizing into structures that block energy burning

Scientists in the US investigating the biological mechanisms behind fat burning have identified a protein that plays a key role in regulating metabolism, and demonstrated how blocking its activity can boost the process in mice. The protein in question, called Them1, is produced within human brown fat in response to temperature, offering researchers a promising new target in their pursuit of more effective treatments for obesity.

The scientists behind the new study had been investigating Them1 for around a decade, intrigued by studies showing how mice produce vast amounts of the protein in their brown fat tissue when subjected to cold temperatures. Unlike white fat tissue that stores the body's excess energy as lipids and leads to love handles and beer bellies, brown fat tissue is quickly burned away by the body to generate heat when we are cold. For this reason, much anti-obesity research centers on efforts to convert white fat into brown.

Looking to build on these earlier studies in mice, the researchers drew up experiments where the rodents were genetically engineered to be lacking Them1. Because they had assumed Them1 was helping the mice generate heat, they expected to find knocking it out would reduce their capacity to do so. But the reverse proved to be true, with mice lacking the protein using up so much energy to produce heat that they actually ate twice as much as typical mice and still lost weight.

“To our complete surprise, when you delete the gene for Them1, the mouse produces more heat, not less,” says study author David Cohen.

In newly published research, the scientists have delved into the reasons behind this unexpected phenomenon. This involved using light and electron microscopes to actually observe Them1 in action on brown fat cells grown in the laboratory, which showed that as the fat begins to burn, the Them1 molecules are chemically altered in a way that causes them to spread out throughout the cell.

One of the effects of this diffusion is that mitochondria, commonly called the powerhouse of the cell, are more readily able to turn the fat stores into energy. As soon as the fat-burning stimulation was halted, the Them1 proteins quickly reorganized into a structure that sits between the mitochondria and fat, once again limiting energy production.

High-resolution imaging shows the Them1 protein at work in brown adipose tissue, organizing into structures that block energy burning
High-resolution imaging shows the Them1 protein at work in brown adipose tissue, organizing into structures that block energy burning

“The study explains a new mechanism that regulates metabolism,” says Cohen. “Them1 hacks the energy pipeline and cuts off the fuel supply to the energy-burning mitochondria. Humans also have brown fat and produce more Them1 in cold conditions, so the findings may have exciting implications for the treatment of obesity.”

In light of these findings, Cohen and his fellow researchers are now working on the development of a drug that inhibits the Them1 protein.

“If we could give humans a drug that inactivates Them1’s energy expenditure-suppressing activity, we might be able to increase fat burning,” he says.

The research was published in the journal Nature Communications.

Source: Beth Israel Deaconess Medical Center, Weill Cornell Medicine

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paul314
So just why do brown fat cell produce so much of this protein? Maybe a safety switch, because it's better to be cold than to starve to death?