study

Clues as to how fat cells work in the body could lead to treatment for type 2 diabetes

by Barbara Hewitt on February 28, 2017

A discovery about what fat cells get up to in the body could lead to a new therapeutic approach for dealing with type 2 diabetes.

Scientists at the Joslin Diabetes Centre in the United States have found that fat cells are not simply big blobs of lipid quietly standing by in the body, instead, they send out hormones and other signalling proteins that affect many types of tissues.

They have now have identified a route by which fat also can deliver a form of small RNAs called microRNAs that helps to regulate other organs.

‘This mechanism may offer the potential to develop an entirely new therapeutic approach,’ said Ronald Kahn, Joslin’s chief academic officer and Mary Iacocca, professor of Medicine at Harvard Medical School.

Kahn explained that the research suggests the possibility of developing gene therapy treatments using fat cells that help in the treatment of type 2 diabetes, obesity, fatty liver disease and some types of cancer.

The scientists used human cells in experiments with mice to study the role of microRNAs, a form of small RNAs that are not translated into proteins but can regulate other RNAS that produce protein.

They are made by all cells in the body, and it is known that some of these microRNAs may be released from the originating cell into the blood. However, exactly what they do once they enter the bloodstream has been debated.

The Joslin scientists focused on microRNAs from fat cells that are released into the blood via tiny sacks called exosomes. They began with a mouse model that was genetically modified so that its fat cells could not create microRNAs.

The Joslin researchers then showed that in these mice which do not make microRNAs in fat, the total population of microRNAs circulating in exosomes dropped significantly. This decrease in circulating miRNAs could be restored when the investigators transplanted normal fat into these mice, a result indicating that many of the microRNAs in circulation were coming from fat.

Next, the scientists studied people with two forms of lipodystrophy, a condition in which fat is lost or genetically not present. In both groups of people, they found that levels of microRNAs circulating in exosomes were lower than normal.

Kahn pointed out that this suggested that these microRNAs generated by fat might aid in diagnostics for metabolic conditions such as obesity, type 2 diabetes and fatty liver disease.

The researchers also found that fat cells engineered to make a certain microRNA that is found in humans, but not mice, could also regulate their target in the livers of the mice. ‘We showed in mice that these circulating microRNAs in exosomes can regulate gene expression, at least in liver and perhaps in other tissues,’ Kahn added.

The team is now looking to see if this microRNA mechanism also works in other tissues such as muscle and brain cells and how the mechanism might be applied in gene therapy.

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