Blocking this protein may keep obesity, diabetes at bay

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Blocking a protein in the liver can prevent obesity and its related diseases — such as type 2 diabetes and fatty liver — in mice, according to new research.

A study by Cincinnati Children’s Hospital Medical Center in Ohio reveals that a protein called Argonaute 2 (AGO2) controls how energy is made and used in the liver.

It does this by silencing RNA, a molecule that carries genetic instructions held in the DNA blueprints in the cell’s nucleus to the cell’s protein-making machinery.

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The scientists revealed that, by silencing RNA, AGO2 slows metabolism in the liver and the organ’s “ability to process a high-fat diet.”

However, when they deleted AGO2 in the livers of mice on a high-fat diet, the mice did not become obese and did not develop type 2 diabetes and fatty liver disease.

Fatty liver disease — or, more accurately, nonalcoholic fatty liver disease — is a condition in which fat builds up in the liver. It can severely harm the organ, whose main job is to clean and detoxify blood.

Vicious cycle in disrupted energy metabolism

The findings suggest that RNA silencing by AGO2 links two important processes: control of energy supply, and the production of proteins inside cells.

“This mechanism,” note the investigators in a recently published Nature Communications paper on their work, “may be the core of a vicious cycle in disrupted energy metabolism in the obese liver.”

The team identified AGO2 after screening and analyzing the behavior of genes and the associated proteins that they target in the liver.

They examined the effect of deleting proteins that play a key role in liver metabolism in normal and genetically engineered mice that were fed on high-fat diets.

Senior study author Takahisa Nakamura, an assistant professor in the Department of Pediatrics at Cincinnati Children’s Hospital, warns that the science is “still basic,” and that it is too early to say how it might translate into new treatments.

There might be important implications, however, for the treatment of “chronic metabolic disorders like diabetes, fatty liver diseases, and other obesity-associated illnesses,” he notes.

What they have achieved so far, Nakamura suggests, should help them search for potential new treatments that target obesity and associated diseases by altering energy balance in the liver.

Further work will involve the confirmation of these findings in “laboratory models” and the development of an experimental AGO2 blocker for clinical testing in humans.

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