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Decoded fat metabolism process: obesity can be switched off

Decoded fat metabolism process: obesity can be switched off


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Newly discovered mechanism prevents obesity

An American research team decoded a metabolic process and discovered a receptor that appears to play a central role in the development of overweight and obesity. In experiments, blocking the receptor meant that overweight could no longer arise and existing overweight was reduced.

Researchers at the Norris Cotton Cancer Center in Dartmouth (USA) found that the aryl hydrocarbon receptor (AHR), which is found in almost all cells, is linked to the development of obesity. Mice that were blocked with this receptor were protected from excessive fat accumulation. Obesity reversed in obese mice with blocked AHR. The results were recently presented in the "International Journal of Obesity".

Obesity has become a global epidemic

Obesity can now be described as a global epidemic. Obese people are at increased risk for many different types of cancer, including breast, colon and pancreatic cancer. Stopping the obesity epidemic could be a crucial help in preventing and treating numerous cancers. Researchers at the Norris Cotton Cancer Center in Dartmouth have now discovered a completely new way of tackling excess fat. Apparently, the ability to store fat can be easily blocked.

Switch off and reverse obesity

The team discovered that a receptor called AHR plays a major role in the body's metabolism. So far, it has only been known that AHR combats intruded environmental chemicals. It has now been shown that AHR also appears to be responsible for the formation of obesity, or at least makes a significant contribution to it. Tests on mice showed that blocking AHR not only prevented obesity, but also reversed obesity.

Despite the high-fat diet, mice did not get fatter

"We ran experiments that showed that despite eating a high-fat diet, mice did not get fatter if they took an active ingredient called α-naphthoflavone (αNF) that is known to block AHR," explains research director Craig Tomlinson. A control group of mice that received the same diet without the drug became very overweight in a short period of time. No adverse effects were observed in the mice who received the drug.

Not only protection, but also repentance

In further studies, the team showed that AHR blockade with αNF not only prevents obesity, but can also reverse it. "In these experiments, we let the mice become obese on a high-fat diet, and then half of the mice were switched to the high-fat diet using the AHR blocker αNF," says Tomlinson. Over the next few weeks, the mice's weight dropped to the same level as that of a control group on a low-fat diet. "No negative effects were observed here either," emphasizes Tomlinson.

Why does AHR blocking have this effect?

Tomlinson's team was able to decipher the underlying mechanism. According to the study, AHR interferes with fat metabolism. If the receptor is blocked, several key genes in liver cells and in fat cells are not induced or activated. In turn, these genes are required for fat storage and fat synthesis, which does not occur due to the lack of activation.

“Few to no studies have shown that obesity can be reversed with drug treatment; the underlying cellular mechanism is even less known, ”says Tomlinson, underlining the importance of the new study.

The therapy should now be tested on people

The researchers have now initiated a clinical study to determine whether AHR can serve as a therapeutic target for reducing obesity in humans. "We are beginning to understand how blocking AHR prevents and reverses obesity, which can lead to therapeutic treatment of obesity in humans," summarizes the study leader. The team also plans to investigate which food components activate the AHR. In addition, the role of AHR in relation to the intestinal bacteria is to be examined in more detail. (vb)

Author and source information

This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.

Graduate editor (FH) Volker Blasek

Swell:

  • Itzel Y. Rojas, Benjamin J. Moyer, Carol S. Ringelberg & Craig R. Tomlinson: Reversal of obesity and liver steatosis in mice via inhibition of aryl hydrocarbon receptor and altered gene expression of CYP1B1, PPARα, SCD1, and osteopontin, International Journal of Obesity, 2020, nature.com
  • Dartmouth's Norris Cotton Cancer Center: New mechanism may safely prevent and reverse obesity (accessed: January 14, 2020), eurekalert.org


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